|
1
|
Ortiz-Hidalgo C. History of Leukemia, Revisited. Curr Oncol Rep 2025:10.1007/s11912-025-01658-2. [PMID: 40106215 DOI: 10.1007/s11912-025-01658-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/27/2025] [Indexed: 03/22/2025]
Abstract
PURPOSE OF THE REVIEW Provide a general historical overview of leukemia, emphasizing the early discoveries that led to its characterization. RECENT FINDINGS Leukemia recognition began in the late 19th century with the advent of the microscope. Leeuwenhoek and Swammerdam described erythrocytes, while Lieutaud first observed globuli albicantes, later identified as lymphocytes by Hewson. Early case studies by Velpeau, Donné, Bennett, Craigie, Virchow, and Fuller suggested that leukocytosis could occur without infection. Virchow coined the term "leukemia," while Bennett proposed "leucocythemia." Neumann identified the bone marrow as the source of blood cells and leukemia, coining the term "myelogenous leukemia," and Ehrlich classified leukemia into myeloid and lymphoid types. In 1914, Boveri linked chromosomal abnormalities to cancer, and in 1960, Nowell and Hungerford discovered the Philadelphia chromosome. The use of mustard gas in WWI led to the development of chemotherapy drugs like chlorambucil and busulfan. The Human Genome Project further advanced leukemia diagnosis and treatment. Leukemia, like many diseases, has evolved due to changes in causative factors such as viruses, bacteria, and genetic mutations, which have impacted its pathogenesis and treatment. It will undoubtedly continue to evolve, with new scientists working towards a cure for this devastating disease.
Collapse
Affiliation(s)
- Carlos Ortiz-Hidalgo
- Department of Anatomical Pathology, Department of Tissue and Cell Biology, School of Medicine, Fundación Clínica Médica Sur, Universidad Panamericana, Mexico City, Mexico.
- Department of Anatomical Pathology, Fundación Clínica Médica Sur, Av. Puente de Piedra 150/Colonia Toriello Guerra Alcaldía Tlalpan, Mexico City, C.P. 14050, Mexico.
| |
Collapse
|
|
2
|
Jaeck S, Depuydt C, Bernard V, Ammar O, Hocké C, Carrière J, Chansel-Debordeaux L. How to Preserve Fertility in Reproductive-Age Women with Cancer. J Clin Med 2025; 14:1912. [PMID: 40142718 PMCID: PMC11942802 DOI: 10.3390/jcm14061912] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2025] [Revised: 03/06/2025] [Accepted: 03/08/2025] [Indexed: 03/28/2025] Open
Abstract
Chemotherapy and radiotherapy, among other gonadotoxic treatments, can significantly affect ovarian reserve and function, potentially leading to premature ovarian insufficiency (POI) and sterility. With the increasing survival rates among young female cancer patients, fertility preservation (FP) has become an essential aspect of cancer care. The decision to pursue FP depends on various factors, including patient age, ovarian reserve, the type of treatment, and its gonadotoxic potential. Several FP strategies are available, including oocyte, embryo, and ovarian tissue cryopreservation. While oocyte and embryo cryopreservation are the gold standard techniques, ovarian tissue cryopreservation and in vitro maturation (IVM) present viable alternatives for patients who cannot undergo ovarian stimulation or for whom stimulation is contraindicated. Despite significant advances within the FP practice, challenges remain in ensuring timely FP counseling, equitable access to services, and optimizing long-term reproductive outcomes. Continued research is needed to refine existing FP techniques, explore innovative approaches, and address ethical considerations in FP decision-making. This review explores current FP options, their clinical applications, and future directions to improve reproductive outcomes in young women undergoing gonadotoxic treatments.
Collapse
Affiliation(s)
- Sébastien Jaeck
- Reproductive Biology Unit-CECOS, University Hospital of Bordeaux, 33000 Bordeaux, France; (S.J.); (C.D.)
| | - Chloé Depuydt
- Reproductive Biology Unit-CECOS, University Hospital of Bordeaux, 33000 Bordeaux, France; (S.J.); (C.D.)
- U1312-BRIC Team Biotherapies Genetics and Oncology-BioGO, Bordeaux University, 33000 Bordeaux, France;
| | - Valérie Bernard
- U1312-BRIC Team Biotherapies Genetics and Oncology-BioGO, Bordeaux University, 33000 Bordeaux, France;
- Gynecological Surgery, Medical Gynecology and Reproductive Medicine Department, University Hospital of Bordeaux, 33000 Bordeaux, France; (C.H.); (J.C.)
| | - Omar Ammar
- Clinical Research and Development Division, Louise, 33300 Bordeaux, France;
| | - Claude Hocké
- Gynecological Surgery, Medical Gynecology and Reproductive Medicine Department, University Hospital of Bordeaux, 33000 Bordeaux, France; (C.H.); (J.C.)
| | - Jennifer Carrière
- Gynecological Surgery, Medical Gynecology and Reproductive Medicine Department, University Hospital of Bordeaux, 33000 Bordeaux, France; (C.H.); (J.C.)
| | - Lucie Chansel-Debordeaux
- Reproductive Biology Unit-CECOS, University Hospital of Bordeaux, 33000 Bordeaux, France; (S.J.); (C.D.)
- U1312-BRIC Team Biotherapies Genetics and Oncology-BioGO, Bordeaux University, 33000 Bordeaux, France;
| |
Collapse
|
|
3
|
Gupta S, Mehra A, Sangwan R. A review on phytochemicals as combating weapon for multidrug resistance in cancer. JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH 2025; 27:107-125. [PMID: 39121374 DOI: 10.1080/10286020.2024.2386678] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/23/2023] [Revised: 07/27/2024] [Accepted: 07/28/2024] [Indexed: 08/11/2024]
Abstract
One can recognize multidrug resistance (MDR) and residue as a biggest difficulty in cancer specialist. Chemotherapy-resistant cancer may be successfully treated by combining MDR-reversing phytochemicals with anticancer drugs. Though, clinical application of phytochemicals either alone or in conjunction with chemotherapy is still in its early stages or requires more research to determine their safety and efficacy. In this review we highlighted topics related to MDR in cancer, including an introduction to subject, mechanism of action of efflux pump, specific proteins involved in drug resistance, altered drug targets, increased drug metabolism, and potential role of phytochemicals in overcoming drug resistance.
Collapse
Affiliation(s)
- Sharwan Gupta
- Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India
| | - Anuradha Mehra
- Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India
| | - Rekha Sangwan
- Department of Pharmaceutical Chemistry, School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India
| |
Collapse
|
|
4
|
Alexander HR, Devi-Chou V. Hepatic Perfusion for Diffuse Metastatic Cancer to the Liver: Open and Percutaneous Techniques. Hematol Oncol Clin North Am 2025; 39:177-190. [PMID: 39510672 DOI: 10.1016/j.hoc.2024.08.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2024]
Abstract
The management of patients with diffuse liver metastases remains a significant clinical challenge. In many cancer patients, metastatic disease may be isolated to the liver or the liver may be the dominant site of progressive metastatic cancer. In this setting, progression of disease in the liver generally is the most significant cause of morbidity and mortality.
Collapse
Affiliation(s)
- H Richard Alexander
- Department of Surgery, Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, 195 Little Albany Street, Room 2009, New Brunswick, NJ 08901, USA.
| | - Virginia Devi-Chou
- Division of Surgical Oncology, Rutgers Cancer Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA
| |
Collapse
|
|
5
|
Gu Y, Yang R, Zhang Y, Guo M, Takehiro K, Zhan M, Yang L, Wang H. Molecular mechanisms and therapeutic strategies in overcoming chemotherapy resistance in cancer. MOLECULAR BIOMEDICINE 2025; 6:2. [PMID: 39757310 PMCID: PMC11700966 DOI: 10.1186/s43556-024-00239-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Revised: 11/26/2024] [Accepted: 12/02/2024] [Indexed: 01/07/2025] Open
Abstract
Cancer remains a leading cause of mortality globally and a major health burden, with chemotherapy often serving as the primary therapeutic option for patients with advanced-stage disease, partially compensating for the limitations of non-curative treatments. However, the emergence of chemotherapy resistance significantly limits its efficacy, posing a major clinical challenge. Moreover, heterogeneity of resistance mechanisms across cancer types complicates the development of universally effective diagnostic and therapeutic approaches. Understanding the molecular mechanisms of chemoresistance and identifying strategies to overcome it are current research focal points. This review provides a comprehensive analysis of the key molecular mechanisms underlying chemotherapy resistance, including drug efflux, enhanced DNA damage repair (DDR), apoptosis evasion, epigenetic modifications, altered intracellular drug metabolism, and the role of cancer stem cells (CSCs). We also examine specific causes of resistance in major cancer types and highlight various molecular targets involved in resistance. Finally, we discuss current strategies aiming at overcoming chemotherapy resistance, such as combination therapies, targeted treatments, and novel drug delivery systems, while proposing future directions for research in this evolving field. By addressing these molecular barriers, this review lays a foundation for the development of more effective cancer therapies aimed at mitigating chemotherapy resistance.
Collapse
Affiliation(s)
- Yixiang Gu
- Department of Biliary-Pancreatic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
- Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Ruifeng Yang
- Department of Urology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China
| | - Yang Zhang
- Department of Biliary-Pancreatic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
- Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China
| | - Miaomiao Guo
- The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, China
| | | | - Ming Zhan
- The Core Laboratory in Medical Center of Clinical Research, State Key Laboratory of Medical Genomics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, China
- Department of Systems Biology, Beckman Research Institute, City of Hope, Monrovia, CA, 91016, USA
| | - Linhua Yang
- Department of Biliary-Pancreatic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
- Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
| | - Hui Wang
- Department of Biliary-Pancreatic Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
- Shanghai Key Laboratory of Biliary Tract Disease, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, China.
| |
Collapse
|
|
6
|
Duffin K, Mitchell RT, Brougham MFH, Hamer G, van Pelt AMM, Mulder CL. Impacts of cancer therapy on male fertility: Past and present. Mol Aspects Med 2024; 100:101308. [PMID: 39265489 DOI: 10.1016/j.mam.2024.101308] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 08/23/2024] [Accepted: 08/30/2024] [Indexed: 09/14/2024]
Abstract
Over the past two decades, advances in cancer therapy have significantly improved survival rates, particularly in childhood cancers. Still, many treatments pose a substantial risk for diminishing future fertility potential due to the gonadotoxic nature of many cancer regimens, justifying fertility preservation programs for both childhood and adult cancer patients. To assure a balance between offering fertility preservation and actual chance of infertility post-treatment, guidelines are in place. However, assessing the actual risk of infertility after treatment remains challenging, given the multi-faceted approach of many cancer treatment plans, which are continuously evolving. This review discusses the evolution of cancer therapy over the past 20 years and attempts to assess their impact on fertility after treatment. Overall, cancer regimens have shifted from broadly killing fast dividing cells to more targeting therapies, reducing collateral damage in general. Although progress has been made to reduce overall toxicity, unfortunately this does not automatically translate to reduced gonadotoxicity. Therefore, current fertility preservation programs continue to be an important part of cancer care.
Collapse
Affiliation(s)
- Kathleen Duffin
- Department of Biomedical Sciences, University of Edinburgh, George Square, Edinburgh, EH8 9XD, UK; Royal Hospital for Children and Young People, 50 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - Rod T Mitchell
- Royal Hospital for Children and Young People, 50 Little France Crescent, Edinburgh, EH16 4TJ, UK; Centre for Reproductive Health, Institute of Regeneration and Repair, University of Edinburgh, 4-5 Little France Drive, Edinburgh BioQuarter, Edinburgh, EH16 4UU, UK
| | - Mark F H Brougham
- Royal Hospital for Children and Young People, 50 Little France Crescent, Edinburgh, EH16 4TJ, UK
| | - Geert Hamer
- Reproductive Biology Laboratory, Center for Reproductive Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, the Netherlands; Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands
| | - Ans M M van Pelt
- Reproductive Biology Laboratory, Center for Reproductive Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, the Netherlands; Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands.
| | - Callista L Mulder
- Reproductive Biology Laboratory, Center for Reproductive Medicine, Amsterdam UMC Location University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, the Netherlands; Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands.
| |
Collapse
|
|
7
|
Seyedi S, Harris VK, Kapsetaki SE, Narayanan S, Saha D, Compton Z, Yousefi R, May A, Fakir E, Boddy AM, Gerlinger M, Wu C, Mina L, Huijben S, Gouge DH, Cisneros L, Ellsworth PC, Maley CC. Resistance Management for Cancer: Lessons from Farmers. Cancer Res 2024; 84:3715-3727. [PMID: 39356625 PMCID: PMC11565176 DOI: 10.1158/0008-5472.can-23-3374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2023] [Revised: 06/29/2024] [Accepted: 09/23/2024] [Indexed: 10/04/2024]
Abstract
One of the main reasons we have not been able to cure cancers is that treatments select for drug-resistant cells. Pest managers face similar challenges with pesticides selecting for pesticide-resistant insects, resulting in similar mechanisms of resistance. Pest managers have developed 10 principles that could be translated to controlling cancers: (i) prevent onset, (ii) monitor continuously, (iii) identify thresholds below which there will be no intervention, (iv) change interventions in response to burden, (v) preferentially select nonchemical control methods, (vi) use target-specific drugs, (vii) use the lowest effective dose, (viii) reduce cross-resistance, (ix) evaluate success based on long-term management, and (x) forecast growth and response. These principles are general to all cancers and cancer drugs and so could be employed broadly to improve oncology. Here, we review the parallel difficulties in controlling drug resistance in pests and cancer cells. We show how the principles of resistance management in pests might be applied to cancer. Integrated pest management inspired the development of adaptive therapy in oncology to increase progression-free survival and quality of life in patients with cancers where cures are unlikely. These pest management principles have the potential to inform clinical trial design.
Collapse
Affiliation(s)
- Sareh Seyedi
- Arizona Cancer Evolution Center, Arizona State University, Tempe, Arizona
- Center for Biocomputing, Security and Society, Biodesign Institute, Arizona State University, Tempe, Arizona
- School of Life Sciences, Arizona State University, Tempe, Arizona
| | - Valerie K. Harris
- Arizona Cancer Evolution Center, Arizona State University, Tempe, Arizona
- Center for Biocomputing, Security and Society, Biodesign Institute, Arizona State University, Tempe, Arizona
| | - Stefania E. Kapsetaki
- Arizona Cancer Evolution Center, Arizona State University, Tempe, Arizona
- Center for Biocomputing, Security and Society, Biodesign Institute, Arizona State University, Tempe, Arizona
| | - Shrinath Narayanan
- Center for Biocomputing, Security and Society, Biodesign Institute, Arizona State University, Tempe, Arizona
- Department of Ecology and Evolution, University of Lausanne, Lausanne, Switzerland
| | - Daniel Saha
- Arizona Cancer Evolution Center, Arizona State University, Tempe, Arizona
- Center for Biocomputing, Security and Society, Biodesign Institute, Arizona State University, Tempe, Arizona
- School of Life Sciences, Arizona State University, Tempe, Arizona
| | - Zachary Compton
- Arizona Cancer Evolution Center, Arizona State University, Tempe, Arizona
- Center for Biocomputing, Security and Society, Biodesign Institute, Arizona State University, Tempe, Arizona
- School of Life Sciences, Arizona State University, Tempe, Arizona
- University of Arizona Cancer Center, University of Arizona College of Medicine, Tucson, Arizona
| | - Rezvan Yousefi
- Arizona Cancer Evolution Center, Arizona State University, Tempe, Arizona
- Center for Biocomputing, Security and Society, Biodesign Institute, Arizona State University, Tempe, Arizona
- The Polytechnic School, Ira A. Fulton Schools of Engineering, Arizona State University, Tempe, Arizona
| | - Alexander May
- Research Casting International, Quinte West, Ontario, Canada
| | - Efe Fakir
- Istanbul University Cerrahpasa School of Medicine, Istanbul, Turkey
| | - Amy M. Boddy
- Arizona Cancer Evolution Center, Arizona State University, Tempe, Arizona
- Exotic Species Cancer Research Alliance, North Carolina State University, Raleigh, North Carolina
- Department of Anthropology, University of California Santa Barbara, Santa Barbara, California
| | - Marco Gerlinger
- Translational Oncogenomics Laboratory, Centre for Evolution and Cancer, The Institute of Cancer Research, London, United Kingdom
- Gastrointestinal Cancer Unit, The Royal Marsden Hospital, London, United Kingdom
| | - Christina Wu
- Division of Hematology and Medical Oncology, Department of Medicine, Mayo Clinic, Phoenix, Arizona
| | | | - Silvie Huijben
- School of Life Sciences, Arizona State University, Tempe, Arizona
- Center for Evolution and Medicine, Arizona State University, Tempe, Arizona
| | - Dawn H. Gouge
- Department of Entomology, University of Arizona, Tucson, Arizona
| | - Luis Cisneros
- Arizona Cancer Evolution Center, Arizona State University, Tempe, Arizona
- Center for Biocomputing, Security and Society, Biodesign Institute, Arizona State University, Tempe, Arizona
- School of Life Sciences, Arizona State University, Tempe, Arizona
| | | | - Carlo C. Maley
- Arizona Cancer Evolution Center, Arizona State University, Tempe, Arizona
- Center for Biocomputing, Security and Society, Biodesign Institute, Arizona State University, Tempe, Arizona
- School of Life Sciences, Arizona State University, Tempe, Arizona
- Center for Evolution and Medicine, Arizona State University, Tempe, Arizona
| |
Collapse
|
|
8
|
Sonkin D, Thomas A, Teicher BA. Cancer treatments: Past, present, and future. Cancer Genet 2024; 286-287:18-24. [PMID: 38909530 PMCID: PMC11338712 DOI: 10.1016/j.cancergen.2024.06.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2024] [Revised: 05/21/2024] [Accepted: 06/15/2024] [Indexed: 06/25/2024]
Abstract
There is a rich history of cancer treatments which provides a number of important lessons for present and future cancer therapies. We outline this history by looking in the past, reviewing the current landscape of cancer treatments, and by glancing at the potential future cancer therapies.
Collapse
Affiliation(s)
- Dmitriy Sonkin
- National Cancer Institute, Division of Cancer Treatment and Diagnosis, Rockville, MD 20850, USA.
| | - Anish Thomas
- National Cancer Institute, Center for Cancer Research, Bethesda, MD 20892, USA
| | - Beverly A Teicher
- National Cancer Institute, Division of Cancer Treatment and Diagnosis, Rockville, MD 20850, USA
| |
Collapse
|
|
9
|
Brycht M, Poltorak L, Baluchová S, Sipa K, Borgul P, Rudnicki K, Skrzypek S. Electrochemistry as a Powerful Tool for Investigations of Antineoplastic Agents: A Comprehensive Review. Crit Rev Anal Chem 2024; 54:1017-1108. [PMID: 35968923 DOI: 10.1080/10408347.2022.2106117] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/15/2022]
Abstract
Cancer is most frequently treated with antineoplastic agents (ANAs) that are hazardous to patients undergoing chemotherapy and the healthcare workers who handle ANAs in the course of their duties. All aspects related to hazardous oncological drugs illustrate that the monitoring of ANAs is essential to minimize the risks associated with these drugs. Among all analytical techniques used to test ANAs, electrochemistry holds an important position. This review, for the first time, comprehensively describes the progress done in electrochemistry of ANAs by means of a variety of bare or modified (bio)sensors over the last four decades (in the period of 1982-2021). Attention is paid not only to the development of electrochemical sensing protocols of ANAs in various biological, environmental, and pharmaceutical matrices but also to achievements of electrochemical techniques in the examination of the interactions of ANAs with deoxyribonucleic acid (DNA), carcinogenic cells, biomimetic membranes, peptides, and enzymes. Other aspects, including the enantiopurity studies, differentiation between single-stranded and double-stranded DNA without using any label or tag, studies on ANAs degradation, and their pharmacokinetics, by means of electrochemical techniques are also commented. Finally, concluding remarks that underline the existence of a significant niche for the basic electrochemical research that should be filled in the future are presented.
Collapse
Affiliation(s)
- Mariola Brycht
- Faculty of Chemistry, Department of Inorganic and Analytical Chemistry, University of Lodz, Lodz, Poland
| | - Lukasz Poltorak
- Faculty of Chemistry, Department of Inorganic and Analytical Chemistry, University of Lodz, Lodz, Poland
| | - Simona Baluchová
- Faculty of Science, Department of Analytical Chemistry, UNESCO Laboratory of Environmental Electrochemistry, Charles University, Prague 2, Czechia
- Department of Precision and Microsystems Engineering, Delft University of Technology, Delft, The Netherlands
| | - Karolina Sipa
- Faculty of Chemistry, Department of Inorganic and Analytical Chemistry, University of Lodz, Lodz, Poland
| | - Paulina Borgul
- Faculty of Chemistry, Department of Inorganic and Analytical Chemistry, University of Lodz, Lodz, Poland
| | - Konrad Rudnicki
- Faculty of Chemistry, Department of Inorganic and Analytical Chemistry, University of Lodz, Lodz, Poland
| | - Sławomira Skrzypek
- Faculty of Chemistry, Department of Inorganic and Analytical Chemistry, University of Lodz, Lodz, Poland
| |
Collapse
|
|
10
|
Bano N, Parveen S, Saeed M, Siddiqui S, Abohassan M, Mir SS. Drug Repurposing of Selected Antibiotics: An Emerging Approach in Cancer Drug Discovery. ACS OMEGA 2024; 9:26762-26779. [PMID: 38947816 PMCID: PMC11209889 DOI: 10.1021/acsomega.4c00617] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 05/19/2024] [Accepted: 05/29/2024] [Indexed: 07/02/2024]
Abstract
Drug repurposing is a method of investigating new therapeutic applications for previously approved medications. This repurposing approach to "old" medications is now highly efficient, simple to arrange, and cost-effective and poses little risk of failure in treating a variety of disorders, including cancer. Drug repurposing for cancer therapy is currently a key topic of study. It is a way of exploring recent therapeutic applications for already-existing drugs. Theoretically, the repurposing strategy has various advantages over the recognized challenges of creating new molecular entities, including being faster, safer, easier, and less expensive. In the real world, several medications have been repurposed, including aspirin, metformin, and chloroquine. However, doctors and scientists address numerous challenges when repurposing drugs, such as the fact that most drugs are not cost-effective and are resistant to bacteria. So the goal of this review is to gather information regarding repurposing pharmaceuticals to make them more cost-effective and harder for bacteria to resist. Cancer patients are more susceptible to bacterial infections. Due to their weak immune systems, antibiotics help protect them from a variety of infectious diseases. Although antibiotics are not immune boosters, they do benefit the defense system by killing bacteria and slowing the growth of cancer cells. Their use also increases the therapeutic efficacy and helps avoid recurrence. Of late, antibiotics have been repurposed as potent anticancer agents because of the evolutionary relationship between the prokaryotic genome and mitochondrial DNA of eukaryotes. Anticancer antibiotics that prevent cancer cells from growing by interfering with their DNA and blocking growth of promoters, which include anthracyclines, daunorubicin, epirubicin, mitoxantrone, doxorubicin, and idarubicin, are another type of FDA-approved antibiotics used to treat cancer. According to the endosymbiotic hypothesis, prokaryotes and eukaryotes are thought to have an evolutionary relationship. Hence, in this study, we are trying to explore antibiotics that are necessary for treating diseases, including cancer, helping people reduce deaths associated with various infections, and substantially extending people's life expectancy and quality of life.
Collapse
Affiliation(s)
- Nilofer Bano
- Molecular
Cell Biology Laboratory, Integral Centre of Excellence for Interdisciplinary
Research (ICEIR-4), Integral University, Kursi Road, Lucknow 226026, India
- Department
of Bioengineering, Faculty of Engineering, Integral University, Kursi Road, Lucknow 226026, India
| | - Sana Parveen
- Molecular
Cell Biology Laboratory, Integral Centre of Excellence for Interdisciplinary
Research (ICEIR-4), Integral University, Kursi Road, Lucknow 226026, India
- Department
of Biosciences, Faculty of Science, Integral
University, Kursi Road, Lucknow 226026, India
| | - Mohd Saeed
- Department
of Biology, College of Sciences, University
of Hail, P.O. Box 2240, Hail 55476, Saudi Arabia
| | - Samra Siddiqui
- Department
of Health Services Management, College of Public Health and Health
Informatics, University of Hail, Hail 55476, Saudi Arabia
| | - Mohammad Abohassan
- Department
of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha 61421, Saudi Arabia
| | - Snober S. Mir
- Molecular
Cell Biology Laboratory, Integral Centre of Excellence for Interdisciplinary
Research (ICEIR-4), Integral University, Kursi Road, Lucknow 226026, India
- Department
of Biosciences, Faculty of Science, Integral
University, Kursi Road, Lucknow 226026, India
| |
Collapse
|
|
11
|
Fahey CC, Rathmell WK. Clinical Trials-Real-World Data to Build a Future for Our Patients. J Clin Oncol 2024; 42:2117-2120. [PMID: 38728618 DOI: 10.1200/jco.24.00374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Revised: 03/11/2024] [Accepted: 03/20/2024] [Indexed: 05/12/2024] Open
Affiliation(s)
- Catherine C Fahey
- Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, Nashville, TN
| | - W Kimryn Rathmell
- National Cancer Institute, National Institutes of Health, Bethesda, MD
| |
Collapse
|
|
12
|
Wang L, Mei Z, Jin G, Liu H, Lv S, Fu R, Li M, Yao C. In situ sustained release hydrogel system delivering GLUT1 inhibitor and chemo-drug for cancer post-surgical treatment. Bioact Mater 2024; 36:541-550. [PMID: 39072288 PMCID: PMC11276927 DOI: 10.1016/j.bioactmat.2024.06.034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 06/10/2024] [Accepted: 06/25/2024] [Indexed: 07/30/2024] Open
Abstract
Systematic administration of small molecular drugs often suffered from the low efficacy and systemic toxicity in cancer therapy. In addition, application of single mode drug usually leads to unsatisfactory therapeutic outcomes. Currently, developing multimodal-drug combination strategy that acts on different pathways without increasing side effects remains great challenge. Here, we developed a hydrogel system that co-delivered glycolysis inhibitor apigenin and chemo-drug gemcitabine to realize combination strategy for combating cancer with minimal systemic toxicity. We demonstrated that this system can not only eliminate tumor cells in situ, but also induce abscopal effect on various tumor models. These results showed that our study provided a safe and effective strategy for clinical cancer treatment.
Collapse
Affiliation(s)
- Lanqing Wang
- Institute of Biomedical Photonics and Sensing, School of Life Science and Technology, Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University, Xi'an, 710049, China
| | - Zi Mei
- School of Stomatology, School of Materials Science and Engineering, Department of General Surgery, Third Hospital, Peking University, Beijing, 100871, China
| | - Guanyu Jin
- School of Stomatology, School of Materials Science and Engineering, Department of General Surgery, Third Hospital, Peking University, Beijing, 100871, China
| | - Hao Liu
- School of Stomatology, School of Materials Science and Engineering, Department of General Surgery, Third Hospital, Peking University, Beijing, 100871, China
| | - Shixian Lv
- School of Stomatology, School of Materials Science and Engineering, Department of General Surgery, Third Hospital, Peking University, Beijing, 100871, China
| | - Runjia Fu
- Department of Oncology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250033, China
| | - Muxing Li
- School of Stomatology, School of Materials Science and Engineering, Department of General Surgery, Third Hospital, Peking University, Beijing, 100871, China
| | - Cuiping Yao
- Institute of Biomedical Photonics and Sensing, School of Life Science and Technology, Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiaotong University, Xi'an, 710049, China
| |
Collapse
|
|
13
|
Day BJ. Oxidative Stress: An Intersection Between Radiation and Sulfur Mustard Lung Injury. Disaster Med Public Health Prep 2024; 18:e86. [PMID: 38706344 PMCID: PMC11218645 DOI: 10.1017/dmp.2023.238] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/07/2024]
Abstract
Nuclear and chemical weapons of mass destruction share both a tragic and beneficial legacy in mankind's history and health. The horrific health effects of ionizing radiation and mustard gas exposures unleashed during disasters, wars, and conflicts have been harnessed to treat human health maladies. Both agents of destruction have been transformed into therapies to treat a wide range of cancers. The discovery of therapeutic uses of radiation and sulfur mustard was largely due to observations by clinicians treating victims of radiation and sulfur mustard gas exposures. Clinicians identified vulnerability of leukocytes to these agents and repurposed their use in the treatment of leukemias and lymphomas. Given the overlap in therapeutic modalities, it goes to reason that there may be common mechanisms to target as protective strategies against their damaging effects. This commentary will highlight oxidative stress as a common mechanism shared by both radiation and sulfur mustard gas exposures and discuss potential therapies targeting oxidative stress as medical countermeasures against the devastating lung diseases wrought by these agents.
Collapse
Affiliation(s)
- Brian J Day
- Department of Medicine, National Jewish Health, Denver, CO, USA
| |
Collapse
|
|
14
|
Parveen M, Karaosmanoglu B, Sucularli C, Uner A, Taskiran EZ, Esendagli G. Acquired immune resistance is associated with interferon signature and modulation of KLF6/c-MYB transcription factors in myeloid leukemia. Eur J Immunol 2024; 54:e2350717. [PMID: 38462943 DOI: 10.1002/eji.202350717] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2023] [Revised: 01/16/2024] [Accepted: 01/16/2024] [Indexed: 03/12/2024]
Abstract
Resistance to immunity is associated with the selection of cancer cells with superior capacities to survive inflammatory reactions. Here, we tailored an ex vivo immune selection model for acute myeloid leukemia (AML) and isolated the residual subpopulations as "immune-experienced" AML (ieAML) cells. We confirmed that upon surviving the immune reactions, the malignant blasts frequently decelerated proliferation, displayed features of myeloid differentiation and activation, and lost immunogenicity. Transcriptomic analyses revealed a limited number of commonly altered pathways and differentially expressed genes in all ieAML cells derived from distinct parental cell lines. Molecular signatures predominantly associated with interferon and inflammatory cytokine signaling were enriched in the AML cells resisting the T-cell-mediated immune reactions. Moreover, the expression and nuclear localization of the transcription factors c-MYB and KLF6 were noted as the putative markers for immune resistance and identified in subpopulations of AML blasts in the patients' bone marrow aspirates. The immune modulatory capacities of ieAML cells lasted for a restricted period when the immune selection pressure was omitted. In conclusion, myeloid leukemia cells harbor subpopulations that can adapt to the harsh conditions established by immune reactions, and a previous "immune experience" is marked with IFN signature and may pave the way for susceptibility to immune intervention therapies.
Collapse
Affiliation(s)
- Mubaida Parveen
- Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara, Türkiye
| | - Beren Karaosmanoglu
- Department of Medical Genetics, Faculty of Medicine, Hacettepe University, Ankara, Türkiye
| | - Ceren Sucularli
- Department of Bioinformatics, Institute of Health Sciences, Hacettepe University, Ankara, Türkiye
| | - Aysegul Uner
- Department of Pathology, Faculty of Medicine, Hacettepe University, Ankara, Türkiye
| | - Ekim Z Taskiran
- Department of Medical Genetics, Faculty of Medicine, Hacettepe University, Ankara, Türkiye
| | - Gunes Esendagli
- Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara, Türkiye
| |
Collapse
|
|
15
|
Li Y. DNA Adducts in Cancer Chemotherapy. J Med Chem 2024; 67:5113-5143. [PMID: 38552031 DOI: 10.1021/acs.jmedchem.3c02476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/12/2024]
Abstract
DNA adducting drugs, including alkylating agents and platinum-containing drugs, are prominent in cancer chemotherapy. Their mechanisms of action involve direct interaction with DNA, resulting in the formation of DNA addition products known as DNA adducts. While these adducts are well-accepted to induce cancer cell death, understanding of their specific chemotypes and their role in drug therapy response remain limited. This perspective aims to address this gap by investigating the metabolic activation and chemical characterization of DNA adducts formed by the U.S. FDA-approved drugs. Moreover, clinical studies on DNA adducts as potential biomarkers for predicting patient responses to drug efficacy are examined. The overarching goal is to engage the interest of medicinal chemists and stimulate further research into the use of DNA adducts as biomarkers for guiding personalized cancer treatment.
Collapse
|
|
16
|
Bercier P, de Thé H. History of Developing Acute Promyelocytic Leukemia Treatment and Role of Promyelocytic Leukemia Bodies. Cancers (Basel) 2024; 16:1351. [PMID: 38611029 PMCID: PMC11011038 DOI: 10.3390/cancers16071351] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Revised: 03/26/2024] [Accepted: 03/27/2024] [Indexed: 04/14/2024] Open
Abstract
The story of acute promyelocytic leukemia (APL) discovery, physiopathology, and treatment is a unique journey, transforming the most aggressive form of leukemia to the most curable. It followed an empirical route fueled by clinical breakthroughs driving major advances in biochemistry and cell biology, including the discovery of PML nuclear bodies (PML NBs) and their central role in APL physiopathology. Beyond APL, PML NBs have emerged as key players in a wide variety of biological functions, including tumor-suppression and SUMO-initiated protein degradation, underscoring their broad importance. The APL story is an example of how clinical observations led to the incremental development of the first targeted leukemia therapy. The understanding of APL pathogenesis and the basis for cure now opens new insights in the treatment of other diseases, especially other acute myeloid leukemias.
Collapse
Affiliation(s)
- Pierre Bercier
- Center for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, Université PSL, 75231 Paris, France;
- GenCellDis, Inserm U944, CNRS UMR7212, Université Paris Cité, 75010 Paris, France
| | - Hugues de Thé
- Center for Interdisciplinary Research in Biology (CIRB), Collège de France, CNRS, INSERM, Université PSL, 75231 Paris, France;
- GenCellDis, Inserm U944, CNRS UMR7212, Université Paris Cité, 75010 Paris, France
- Hematology Laboratory, Hôpital St Louis, AP/HP, 75010 Paris, France
| |
Collapse
|
|
17
|
Timofeev O, Giron P, Lawo S, Pichler M, Noeparast M. ERK pathway agonism for cancer therapy: evidence, insights, and a target discovery framework. NPJ Precis Oncol 2024; 8:70. [PMID: 38485987 PMCID: PMC10940698 DOI: 10.1038/s41698-024-00554-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Accepted: 02/16/2024] [Indexed: 03/18/2024] Open
Abstract
At least 40% of human cancers are associated with aberrant ERK pathway activity (ERKp). Inhibitors targeting various effectors within the ERKp have been developed and explored for over two decades. Conversely, a substantial body of evidence suggests that both normal human cells and, notably to a greater extent, cancer cells exhibit susceptibility to hyperactivation of ERKp. However, this vulnerability of cancer cells remains relatively unexplored. In this review, we reexamine the evidence on the selective lethality of highly elevated ERKp activity in human cancer cells of varying backgrounds. We synthesize the insights proposed for harnessing this vulnerability of ERK-associated cancers for therapeutical approaches and contextualize these insights within established pharmacological cancer-targeting models. Moreover, we compile the intriguing preclinical findings of ERK pathway agonism in diverse cancer models. Lastly, we present a conceptual framework for target discovery regarding ERKp agonism, emphasizing the utilization of mutual exclusivity among oncogenes to develop novel targeted therapies for precision oncology.
Collapse
Affiliation(s)
- Oleg Timofeev
- Institute of Molecular Oncology, Member of the German Center for Lung Research (DZL), Philipps University, 35043, Marburg, Germany
| | - Philippe Giron
- Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Clinical Sciences, Research group Genetics, Reproduction and Development, Centre for Medical Genetics, Laarbeeklaan 101, 1090, Brussels, Belgium
| | - Steffen Lawo
- CRISPR Screening Core Facility, Max Planck Institute for Biology of Ageing, 50931, Cologne, Germany
| | - Martin Pichler
- Translational Oncology, II. Med Clinics Hematology and Oncology, 86156, Augsburg, Germany
| | - Maxim Noeparast
- Translational Oncology, II. Med Clinics Hematology and Oncology, 86156, Augsburg, Germany.
| |
Collapse
|
|
18
|
Yang Z, Liu S, Pan X. Research progress on mitochondrial damage and repairing in oocytes: A review. Mitochondrion 2024; 75:101845. [PMID: 38237648 DOI: 10.1016/j.mito.2024.101845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2023] [Revised: 01/04/2024] [Accepted: 01/14/2024] [Indexed: 01/26/2024]
Abstract
Oocytes are the female germ cells, which are susceptible to stress stimuli. The development of oocytes in the ovary is affected by many environmental and metabolic factors, food toxins, aging, and pathological factors. Mitochondria are the main target organelles of these factors, and the damage to mitochondrial structure and function can affect the production of ATP, the regulation of redox reactions, and apoptosis in oocytes. Mitochondrial damage is closely related to the decrease in oocyte quality and is the main factor leading to female infertility. Antioxidant foods or drugs have been used to prevent mitochondrial damage from some stressors or to repair damaged mitochondria, thereby improving oocyte development and female reproductive outcomes. In this paper, the damage of mitochondria during oocyte development by the above factors has been reviewed, and the relevant measures to alleviate the damage of mitochondria in oocytes have been discussed. Our findings may provide a theoretical basis and experimental basis for improving female fertility.
Collapse
Affiliation(s)
- Zheqing Yang
- Center for Reproductive Medicine, Jilin Medical University, Jilin 132013, Jilin, China
| | - Sitong Liu
- Department of Anatomy, Jilin Medical University, Jilin 132013, Jilin, China
| | - Xiaoyan Pan
- Center for Reproductive Medicine, Jilin Medical University, Jilin 132013, Jilin, China.
| |
Collapse
|
|
19
|
Mathur S, Karumban KS, Muley A, Tuti N, Shaji UP, Roy I, Verma A, Kumawat MK, Roy A, Maji S. Chromophore appended DPA-based copper(II) complexes with a diimine motif towards DNA binding and fragmentation studies. Dalton Trans 2024; 53:1163-1177. [PMID: 38105760 DOI: 10.1039/d3dt01864d] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2023]
Abstract
Mixed ligand copper(II) complexes [Cu(L1)(bpy)](ClO4)21 and [Cu(L2)(bpy)](ClO4)22 (where L1 = 1-(anthracen-9-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine, L2 = 1-(pyren-1-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine and bpy = 2,2'-bipyridine) were synthesised and characterised thoroughly via different analytical and spectroscopic techniques i.e., UV-vis spectroscopy, fluorescence spectroscopy, FT-IR spectroscopy, HRMS and EPR spectroscopy. The molecular structures of the synthesised complexes were obtained using the single-crystal X-ray diffraction technique. Both complexes exhibited penta-coordinated and acquired distorted square pyramidal geometry. The redox behaviour of complexes 1 and 2 was investigated by employing cyclic voltammetry. The DNA binding study was carried out by UV-vis spectrophotometry using double-stranded salmon sperm DNA (ds-ss-DNA). The binding constant (Kb) values of 1 and 2 were 0.11 × 104 M-1 and 1.05 × 104 M-1, respectively, which indicates that 2 has better binding ability than 1. This might be due to the higher conjugative abilities with the extended surface area of the aromatic pyrene ring compared to the anthracene moiety. The fluorescence quenching experiments were also performed with EB bound DNA (EB-DNA) and Stern-Volmer constant (KSV) values were calculated as 1.23 × 105 M-1 and 1.39 × 105 M-1 for 1 and 2, respectively, suggesting that 2 showed stronger interaction with ss-DNA than 1. The molecular docking data support the DNA-binding studies, with the sites and mode of interactions against B-DNA varying with 1 and 2. Evaluation of the DNA binding properties of the complexes to linearized plasmid DNA indicated that 2 had modest DNA binding properties, which is a pre-requisite for a genotoxic agent. The effect of 1 and 2 on cell survival was analysed using HeLa cells by MTT assay and it was observed that the IC50 values of 1 and 2 were 43.7 μM and 18.6 μM, respectively. Our study paves the way for the designing of bio-inspired novel mixed metal complexes, which shows promising results for further exploration of molecular and mechanistic studies towards the development of non-platinum based economical metallodrugs.
Collapse
Affiliation(s)
- Shobhit Mathur
- Department of Chemistry, Indian Institute of Technology, Hyderabad, Kandi, Sangareddy 502284, Telangana, India.
| | - Kalai Selvan Karumban
- Department of Chemistry, Indian Institute of Technology, Hyderabad, Kandi, Sangareddy 502284, Telangana, India.
| | - Arabinda Muley
- Department of Chemistry, Indian Institute of Technology, Hyderabad, Kandi, Sangareddy 502284, Telangana, India.
| | - Nikhil Tuti
- Department of Biotechnology, Indian Institute of Technology, Hyderabad, Kandi, Sangareddy 502284, Telangana, India.
| | | | - Indrajit Roy
- Department of Chemistry, Indian Institute of Technology, Hyderabad, Kandi, Sangareddy 502284, Telangana, India.
| | - Anushka Verma
- Department of Chemistry, Indian Institute of Technology, Hyderabad, Kandi, Sangareddy 502284, Telangana, India.
| | - Manoj Kumar Kumawat
- Department of Chemistry, Indian Institute of Technology, Hyderabad, Kandi, Sangareddy 502284, Telangana, India.
| | - Anindya Roy
- Department of Biotechnology, Indian Institute of Technology, Hyderabad, Kandi, Sangareddy 502284, Telangana, India.
| | - Somnath Maji
- Department of Chemistry, Indian Institute of Technology, Hyderabad, Kandi, Sangareddy 502284, Telangana, India.
| |
Collapse
|
|
20
|
Tangsiri M, Hheidari A, Liaghat M, Razlansari M, Ebrahimi N, Akbari A, Varnosfaderani SMN, Maleki-Sheikhabadi F, Norouzi A, Bakhtiyari M, Zalpoor H, Nabi-Afjadi M, Rahdar A. Promising applications of nanotechnology in inhibiting chemo-resistance in solid tumors by targeting epithelial-mesenchymal transition (EMT). Biomed Pharmacother 2024; 170:115973. [PMID: 38064969 DOI: 10.1016/j.biopha.2023.115973] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 11/25/2023] [Accepted: 11/29/2023] [Indexed: 01/10/2024] Open
Abstract
The resistance of cancer cells to chemotherapy, also known as chemo-resistance, poses a significant obstacle to cancer treatment and can ultimately result in patient mortality. Epithelial-mesenchymal transition (EMT) is one of the many factors and processes responsible for chemo-resistance. Studies have shown that targeting EMT can help overcome chemo-resistance, and nanotechnology and nanomedicine have emerged as promising approaches to achieve this goal. This article discusses the potential of nanotechnology in inhibiting EMT and proposes a viable strategy to combat chemo-resistance in various solid tumors, including breast cancer, lung cancer, pancreatic cancer, glioblastoma, ovarian cancer, gastric cancer, and hepatocellular carcinoma. While nanotechnology has shown promising results in targeting EMT, further research is necessary to explore its full potential in overcoming chemo-resistance and discovering more effective methods in the future.
Collapse
Affiliation(s)
- Mona Tangsiri
- Department of Medical Entomology and Vector Control, School of Health, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Hheidari
- Department of Mechanical Engineering, Islamic Azad University, Science and Research Branch, Tehran, Iran
| | - Mahsa Liaghat
- Department of Medical Laboratory sciences, Faculty of Medical Sciences, Kazerun Branch, Islamic Azad University, Kazerun, Iran; Network of Immunity in Infection, Malignancy & Autoimmunity (NIIMA), Universal Scientific Education & Research Network (USERN), Tehran, Iran
| | - Mahtab Razlansari
- Faculty of Mathematics and Natural Sciences, Tübingen University, Tübingen 72076, Germany
| | - Narges Ebrahimi
- Immunology Research Center, Institute of Immunology and Infectious Diseases, Iran University of Medical Sciences, Tehran, Iran
| | - Abdullatif Akbari
- Network of Immunity in Infection, Malignancy & Autoimmunity (NIIMA), Universal Scientific Education & Research Network (USERN), Tehran, Iran; Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | | | - Fahimeh Maleki-Sheikhabadi
- Department of Hematology and Blood Banking, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ali Norouzi
- Dental Research Center, Faculty of Dentistry, Mazandaran University of Medical Sciences, Sari, Iran
| | - Maryam Bakhtiyari
- Network of Immunity in Infection, Malignancy & Autoimmunity (NIIMA), Universal Scientific Education & Research Network (USERN), Tehran, Iran; Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
| | - Hamidreza Zalpoor
- Network of Immunity in Infection, Malignancy & Autoimmunity (NIIMA), Universal Scientific Education & Research Network (USERN), Tehran, Iran; Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Mohsen Nabi-Afjadi
- Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.
| | - Abbas Rahdar
- Department of Physics, University of Zabol, Zabol 98613-35856, Iran.
| |
Collapse
|
|
21
|
Sharma S, Sharma H, Gogoi H. Bacterial immunotherapy: is it a weapon in our arsenal in the fight against cancer? Front Immunol 2023; 14:1277677. [PMID: 38090593 PMCID: PMC10711065 DOI: 10.3389/fimmu.2023.1277677] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2023] [Accepted: 11/03/2023] [Indexed: 12/18/2023] Open
Abstract
Advances in understanding the genetic basis of cancer have driven alternative treatment approaches. Recent findings have demonstrated the potential of bacteria and it's components to serve as robust theranostic agents for cancer eradication. Compared to traditional cancer therapies like surgery, chemotherapy, radiotherapy, bacteria mediated tumor therapy has exhibited superior cancer suppressing property which is attributed a lot to it's tumor proliferating and accumulating characteristics. Genetically modified bacteria has reduced inherent toxicity and enhanced specificity towards tumor microenvironment. This anti- tumor activity of bacteria is attributed to its toxins and other active components from the cell membrane, cell wall and spores. Furthermore, bacterial genes can be regulated to express and deliver cytokines, antibodies and cancer therapeutics. Although there is less clinical data available, the pre- clinical research clearly indicates the feasibility and potential of bacteria- mediated cancer therapy.
Collapse
Affiliation(s)
- Shubhra Sharma
- Amity Institute of Microbial Technology, Amity University Rajasthan, Jaipur, India
| | - Himani Sharma
- Amity Institute of Microbial Technology, Amity University Rajasthan, Jaipur, India
| | - Himanshu Gogoi
- Amity Institute of Microbial Technology, Amity University Rajasthan, Jaipur, India
- Translational Health Science and Technology Institute, National Capital Region (NCR) Biotech Science Cluster, Faridabad, India
| |
Collapse
|
|
22
|
Ceniceros A, Cañedo L, Méndez C, Olano C, Schleissner C, Cuevas C, de la Calle F, Salas JA. Identification of the Biosynthetic Gene Cluster of New Piperazic Acid-Containing Lipopeptides with Cytotoxic Activity in the Genome of Marine Streptomyces PHM034. Metabolites 2023; 13:1091. [PMID: 37887416 PMCID: PMC10609185 DOI: 10.3390/metabo13101091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Revised: 10/10/2023] [Accepted: 10/17/2023] [Indexed: 10/28/2023] Open
Abstract
Three novel lipopeptides, PM130391 (1), PM130392 (2), and PM140293 (3) were obtained from cultures of Streptomyces tuirus PHM034 isolated from a marine sediment. Structural elucidation of the three compounds showed they belong to the nonribosomal peptides family, and they all contain an acylated alanine, three piperazic acids, a methylated glycine, and an N-hydroxylated alanine. The difference between the three compounds resides in the acyl chain bound to the alanine residue. All three compounds showed cytotoxic activity against human cancer cell lines. Genome sequence and bioinformatics analysis allowed the identification of the gene cluster responsible for the biosynthesis. Inactivation of a nonribosomal peptide synthase of this cluster abolished the biosynthesis of the three compounds, thus demonstrating the involvement of this cluster in the biosynthesis of these lipopeptides.
Collapse
Affiliation(s)
- Ana Ceniceros
- Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain; (A.C.); (C.M.); (C.O.)
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33006 Oviedo, Spain
| | - Librada Cañedo
- Drug Discovery Area, PharmaMar S.A. Avda. de los Reyes 1, Colmenar Viejo, 28770 Madrid, Spain; (L.C.); (C.C.); (F.d.l.C.)
| | - Carmen Méndez
- Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain; (A.C.); (C.M.); (C.O.)
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33006 Oviedo, Spain
| | - Carlos Olano
- Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain; (A.C.); (C.M.); (C.O.)
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33006 Oviedo, Spain
| | - Carmen Schleissner
- Unolab Manufacturing, Avenida de las Flores 6, Humanes de Madrid, 28970 Madrid, Spain;
| | - Carmen Cuevas
- Drug Discovery Area, PharmaMar S.A. Avda. de los Reyes 1, Colmenar Viejo, 28770 Madrid, Spain; (L.C.); (C.C.); (F.d.l.C.)
| | - Fernando de la Calle
- Drug Discovery Area, PharmaMar S.A. Avda. de los Reyes 1, Colmenar Viejo, 28770 Madrid, Spain; (L.C.); (C.C.); (F.d.l.C.)
| | - José A. Salas
- Departamento de Biología Funcional e Instituto Universitario de Oncología del Principado de Asturias (IUOPA), Universidad de Oviedo, 33006 Oviedo, Spain; (A.C.); (C.M.); (C.O.)
- Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33006 Oviedo, Spain
| |
Collapse
|
|
23
|
Schulz JA, Hartz AMS, Bauer B. ABCB1 and ABCG2 Regulation at the Blood-Brain Barrier: Potential New Targets to Improve Brain Drug Delivery. Pharmacol Rev 2023; 75:815-853. [PMID: 36973040 PMCID: PMC10441638 DOI: 10.1124/pharmrev.120.000025] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Revised: 03/10/2023] [Accepted: 03/10/2023] [Indexed: 03/29/2023] Open
Abstract
The drug efflux transporters ABCB1 and ABCG2 at the blood-brain barrier limit the delivery of drugs into the brain. Strategies to overcome ABCB1/ABCG2 have been largely unsuccessful, which poses a tremendous clinical problem to successfully treat central nervous system (CNS) diseases. Understanding basic transporter biology, including intracellular regulation mechanisms that control these transporters, is critical to solving this clinical problem.In this comprehensive review, we summarize current knowledge on signaling pathways that regulate ABCB1/ABCG2 at the blood-brain barrier. In Section I, we give a historical overview on blood-brain barrier research and introduce the role that ABCB1 and ABCG2 play in this context. In Section II, we summarize the most important strategies that have been tested to overcome the ABCB1/ABCG2 efflux system at the blood-brain barrier. In Section III, the main component of this review, we provide detailed information on the signaling pathways that have been identified to control ABCB1/ABCG2 at the blood-brain barrier and their potential clinical relevance. This is followed by Section IV, where we explain the clinical implications of ABCB1/ABCG2 regulation in the context of CNS disease. Lastly, in Section V, we conclude by highlighting examples of how transporter regulation could be targeted for therapeutic purposes in the clinic. SIGNIFICANCE STATEMENT: The ABCB1/ABCG2 drug efflux system at the blood-brain barrier poses a significant problem to successful drug delivery to the brain. The article reviews signaling pathways that regulate blood-brain barrier ABCB1/ABCG2 and could potentially be targeted for therapeutic purposes.
Collapse
Affiliation(s)
- Julia A Schulz
- Department of Pharmaceutical Sciences, College of Pharmacy (J.A.S., B.B.), Sanders-Brown Center on Aging and Department of Pharmacology and Nutritional Sciences, College of Medicine (A.M.S.H.), University of Kentucky, Lexington, Kentucky
| | - Anika M S Hartz
- Department of Pharmaceutical Sciences, College of Pharmacy (J.A.S., B.B.), Sanders-Brown Center on Aging and Department of Pharmacology and Nutritional Sciences, College of Medicine (A.M.S.H.), University of Kentucky, Lexington, Kentucky
| | - Björn Bauer
- Department of Pharmaceutical Sciences, College of Pharmacy (J.A.S., B.B.), Sanders-Brown Center on Aging and Department of Pharmacology and Nutritional Sciences, College of Medicine (A.M.S.H.), University of Kentucky, Lexington, Kentucky
| |
Collapse
|
|
24
|
Verma J, Warsame C, Seenivasagam RK, Katiyar NK, Aleem E, Goel S. Nanoparticle-mediated cancer cell therapy: basic science to clinical applications. Cancer Metastasis Rev 2023; 42:601-627. [PMID: 36826760 PMCID: PMC10584728 DOI: 10.1007/s10555-023-10086-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2022] [Accepted: 01/16/2023] [Indexed: 02/25/2023]
Abstract
Every sixth person in the world dies due to cancer, making it the second leading severe cause of death after cardiovascular diseases. According to WHO, cancer claimed nearly 10 million deaths in 2020. The most common types of cancers reported have been breast (lung, colon and rectum, prostate cases), skin (non-melanoma) and stomach. In addition to surgery, the most widely used traditional types of anti-cancer treatment are radio- and chemotherapy. However, these do not distinguish between normal and malignant cells. Additional treatment methods have evolved over time for early detection and targeted therapy of cancer. However, each method has its limitations and the associated treatment costs are quite high with adverse effects on the quality of life of patients. Use of individual atoms or a cluster of atoms (nanoparticles) can cause a paradigm shift by virtue of providing point of sight sensing and diagnosis of cancer. Nanoparticles (1-100 nm in size) are 1000 times smaller in size than the human cell and endowed with safer relocation capability to attack mechanically and chemically at a precise location which is one avenue that can be used to destroy cancer cells precisely. This review summarises the extant understanding and the work done in this area to pave the way for physicians to accelerate the use of hybrid mode of treatments by leveraging the use of various nanoparticles.
Collapse
Affiliation(s)
- Jaya Verma
- School of Engineering, London South Bank University, London, SE10AA UK
| | - Caaisha Warsame
- School of Engineering, London South Bank University, London, SE10AA UK
| | | | | | - Eiman Aleem
- School of Applied Sciences, Division of Human Sciences, Cancer Biology and Therapy Research Group, London South Bank University, London, SE10AA UK
| | - Saurav Goel
- School of Engineering, London South Bank University, London, SE10AA UK
- Department of Mechanical Engineering, University of Petroleum and Energy Studies, Dehradun, 248007 India
| |
Collapse
|
|
25
|
Guidolin V, Jacobs FC, MacMillan ML, Villalta PW, Balbo S. Liquid Chromatography-Mass Spectrometry Screening of Cyclophosphamide DNA Damage In Vitro and in Patients Undergoing Chemotherapy Treatment. Chem Res Toxicol 2023; 36:1278-1289. [PMID: 37490747 PMCID: PMC11231964 DOI: 10.1021/acs.chemrestox.3c00008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/27/2023]
Abstract
DNA alkylating drugs have been used as frontline medications to treat cancer for decades. Their chemical reaction with DNA leads to the blockage of DNA replication, which impacts cell replication. While this impacts rapidly dividing cancerous cells, this process is not selective and results in highly variable and often severe side effects in patients undergoing alkylating-drug based therapies. The development of biomarkers to identify patients who effectively respond with tolerable toxicities vs patients who develop serious side effects is needed. Cyclophosphamide (CPA) is a commonly used chemotherapeutic drug and lacks biomarkers to evaluate its therapeutic effect and toxicity. Upon administration, CPA is metabolically activated and converted to phosphoramide mustard and acrolein, which are responsible for its efficacy and toxicity, respectively. Previous studies have explored the detection of the major DNA adduct of CPA, the interstrand DNA-DNA cross-link G-NOR-G, finding differences in the cross-link amount between Fanconi Anemia and non-Fanconi Anemia patients undergoing chemotherapy treatment. In this study, we take advantage of our DNA adductomic approach to comprehensively profile CPA's and its metabolites' reactions with DNA in vitro and in patients undergoing CPA-based chemotherapy. This investigation led to the detection of 40 DNA adducts in vitro and 20 DNA adducts in patients treated with CPA. Moreover, acrolein-derived DNA adducts were quantified in patient samples. The results suggest that CPA-DNA damage is very complex, and an evaluation of DNA adduct profiles is necessary when evaluating the relationship between CPA-DNA damage and patient outcome.
Collapse
Affiliation(s)
- Valeria Guidolin
- Masonic Cancer Center, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, United States
- School of Public Health, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, United States
| | - Foster C. Jacobs
- Masonic Cancer Center, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, United States
- School of Public Health, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, United States
| | - Margaret L. MacMillan
- Masonic Cancer Center, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, United States
- Blood and Marrow Transplantation & Cellular Therapy Program, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, United States
| | - Peter W. Villalta
- Masonic Cancer Center, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, United States
- Department of Medicinal Chemistry, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, United States
| | - Silvia Balbo
- Masonic Cancer Center, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, United States
- School of Public Health, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, United States
| |
Collapse
|
|
26
|
Mendes I, Vale N. How Can the Microbiome Induce Carcinogenesis and Modulate Drug Resistance in Cancer Therapy? Int J Mol Sci 2023; 24:11855. [PMID: 37511612 PMCID: PMC10380870 DOI: 10.3390/ijms241411855] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 07/18/2023] [Accepted: 07/21/2023] [Indexed: 07/30/2023] Open
Abstract
Over the years, cancer has been affecting the lives of many people globally and it has become one of the most studied diseases. Despite the efforts to understand the cell mechanisms behind this complex disease, not every patient seems to respond to targeted therapies or immunotherapies. Drug resistance in cancer is one of the limiting factors contributing to unsuccessful therapies; therefore, understanding how cancer cells acquire this resistance is essential to help cure individuals affected by cancer. Recently, the altered microbiome was observed to be an important hallmark of cancer and therefore it represents a promising topic of cancer research. Our review aims to provide a global perspective of some cancer hallmarks, for instance how genetic and epigenetic modifications may be caused by an altered human microbiome. We also provide information on how an altered human microbiome can lead to cancer development as well as how the microbiome can influence drug resistance and ultimately targeted therapies. This may be useful to develop alternatives for cancer treatment, i.e., future personalized medicine that can help in cases where traditional cancer treatment is unsuccessful.
Collapse
Affiliation(s)
- Inês Mendes
- OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal;
- CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal
- School of Life and Environmental Sciences, University of Trás-os-Montes and Alto Douro (UTAD), Edifício de Geociências, 5000-801 Vila Real, Portugal
| | - Nuno Vale
- OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal;
- CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal
- Department of Community Medicine, Information and Health Decision Sciences (MEDCIDS), Faculty of Medicine, University of Porto, Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal
| |
Collapse
|
|
27
|
Bruchelt G, Klose C, Lischka M, Brandes M, Handgretinger R, Brueckner R. Hybrid Molecules of Benzylguanidine and the Alkylating Group of Melphalan: Synthesis and Effects on Neuroblastoma Cells. J Clin Med 2023; 12:4469. [PMID: 37445504 DOI: 10.3390/jcm12134469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 06/15/2023] [Accepted: 06/27/2023] [Indexed: 07/15/2023] Open
Abstract
The therapy of neuroblastoma relies, amongst other things, on administering chemotherapeutics and radioactive compounds, e.g., the (meta-iodobenzyl)guanidine [131I]mIBG. For special applications (conditioning before stem cell transplantation), busulfan and melphalan (M) proved to be effective. However, both drugs are not used for normal chemotherapy in neuroblastoma because of their side effects. The alkylating drug melphalan contains a (Cl-CH2-CH2-)2N- group in the para-position of the phenyl moiety of the essential amino acid phenylalanine (Phe) and can, therefore, be taken up by virtually all kinds of cells by amino acid transporters. In contrast, mIBG isotopologs are taken up more selectively by neuroblastoma cells via the noradrenaline transporter (NAT). The present study aimed at synthesising and studying hybrid molecules of benzylguanidine (BG) and the alkylating motif of M. Such hybrids should combine the preferential uptake of BGs into neuroblastoma cells with the cytotoxicity of M. Besides the hybrid of BG with the dialkylating group (Cl-CH2-CH2-)2N- bound in the para-position as in M (pMBG), we also synthesised mMBG, which is BG meta-substituted by a (Cl-CH2-CH2-)2N- group. Furthermore, two monoalkylating hybrid molecules were synthesised: the BG para-substituted by a (Cl-CH2-CH2-)NH- group (pM*BG) and the BG meta-substituted by a (Cl-CH2-CH2-)NH- group (mM*BG). The effects of the four new compounds were studied with human neuroblastoma cell lines (SK-N-SH, Kelly, and LS) with regard to uptake, viability, and proliferation by standard test systems. The dialkylating hybrid molecules pMBG and mMBG were at least as effective as M, whereas the monoalkylating hybrid molecules pM*BG and mM*BG were more effective than M. Considering the preferred uptake via the noradrenaline transporter by neuroblastoma cells, we conclude that they might be well suited for therapy.
Collapse
Affiliation(s)
- Gernot Bruchelt
- Children's University Hospital, Hoppe-Seyler-Str. 1, D-72076 Tuebingen, Germany
| | - Chihab Klose
- Children's University Hospital, Hoppe-Seyler-Str. 1, D-72076 Tuebingen, Germany
| | - Matthias Lischka
- Institute of Organic Chemistry, Albert-Ludwigs-University, Albertstr. 21, D-79104 Freiburg, Germany
| | - Marietta Brandes
- Children's University Hospital, Hoppe-Seyler-Str. 1, D-72076 Tuebingen, Germany
| | | | - Reinhard Brueckner
- Institute of Organic Chemistry, Albert-Ludwigs-University, Albertstr. 21, D-79104 Freiburg, Germany
| |
Collapse
|
|
28
|
Wang M. Targeting leukemia with a metabolic genotoxin. Blood 2023; 141:2293-2295. [PMID: 37166927 DOI: 10.1182/blood.2022019509] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/12/2023] Open
|
|
29
|
Rejeski K, Greco R, Onida F, Sánchez-Ortega I, Bonini C, Sureda A, Gribben JG, Yakoub-Agha I, Subklewe M. An International Survey on Grading, Diagnosis, and Management of Immune Effector Cell-Associated Hematotoxicity (ICAHT) Following CAR T-cell Therapy on Behalf of the EBMT and EHA. Hemasphere 2023; 7:e889. [PMID: 37125259 PMCID: PMC10145722 DOI: 10.1097/hs9.0000000000000889] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2023] [Accepted: 04/06/2023] [Indexed: 05/02/2023] Open
Abstract
Hematological toxicity represents the most common grade ≥3 toxicity after chimeric antigen receptor (CAR) T-cell therapy. However, its underlying pathophysiology is incompletely understood and its grading and management remains ill-defined. To inform the forthcoming European Hematology Association/European Society for Blood and Marrow Transplantation (EHA/EBMT) guidelines on the management of "immune effector cell-associated hematotoxicity" (ICAHT), we undertook a survey of experienced clinicians using an online survey focusing on (1) grading, (2) risk-stratification and diagnostic work-up, (3) short-term, and (4) long-term management of ICAHT. There were 81 survey respondents across 18 countries. A high degree of variability was noted for cytopenia grading in regards to depth, duration, and time from CAR-T infusion. The majority of experts favored pre-CAR-T bone marrow studies, especially in case of a high-risk profile. Most respondents felt that the work-up for patients with severe hematotoxicity should rule-out viral infections (96%), substrate deficiency (80%), or coincident sHLH/MAS (serum ferritin, 92%), and should include bone marrow aspiration (86%) and/or biopsy (61%). Clinicians were divided as to whether the occurrence of coincident immunotoxicity should influence the decision to apply G-CSF, and when to initiate G-CSF support. In case of prolonged thrombocytopenia, most survey participants favored thrombopoietin agonists (86%). Conversely, autologous hematopoietic cell boosts represented the preferred choice for neutropenia (63%), although they were frequently not available and no consensus was reached regarding the optimal trigger point. These findings underline the current heterogeneity of practice patterns regarding ICAHT and invite the development of consensus guidelines, which may harmonize grading, establish standard operating procedures for diagnosis, and set management guidelines.
Collapse
Affiliation(s)
- Kai Rejeski
- Department of Medicine III – Hematology/Oncology, University Hospital, LMU Munich, Germany
| | - Raffaella Greco
- Unit of Hematology and Bone Marrow Transplantation, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Francesco Onida
- Hematology and BMT Unit, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of Milan, Italy
| | - Isabel Sánchez-Ortega
- European Society for Blood and Marrow Transplantation (EBMT) Executive Office, Barcelona, Spain
| | - Chiara Bonini
- Experimental Hematology Unit, Division of Immunology, Transplantation and Infectious Diseases, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele Scientific Institute, Milan, Italy
| | - Anna Sureda
- Institut Català d’Oncologia-Hospital Duran i Reynals, Barcelona, Spain
| | - John G. Gribben
- Centre for Haemato-Oncology, Barts Cancer Institute, Queen Mary University London, United Kingdom
| | | | - Marion Subklewe
- Department of Medicine III – Hematology/Oncology, University Hospital, LMU Munich, Germany
| |
Collapse
|
|
30
|
Ifosfamide - History, efficacy, toxicity and encephalopathy. Pharmacol Ther 2023; 243:108366. [PMID: 36842616 DOI: 10.1016/j.pharmthera.2023.108366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2023] [Revised: 02/16/2023] [Accepted: 02/21/2023] [Indexed: 02/26/2023]
Abstract
In this review we trace the passage of fundamental ideas through 20th century cancer research that began with observations on mustard gas toxicity in World War I. The transmutation of these ideas across scientific and national boundaries, was channeled from chemical carcinogenesis labs in London via Yale and Chicago, then ultimately to the pharmaceutical industry in Bielefeld, Germany. These first efforts to checkmate cancer with chemicals led eventually to the creation of one of the most successful groups of cancer chemotherapeutic drugs, the oxazaphosphorines, first cyclophosphamide (CP) in 1958 and soon thereafter its isomer ifosfamide (IFO). The giant contributions of Professor Sir Alexander Haddow, Dr. Alfred Z. Gilman & Dr. Louis S. Goodman, Dr. George Gomori and Dr. Norbert Brock step by step led to this breakthrough in cancer chemotherapy. A developing understanding of the metabolic disposition of ifosfamide directed efforts to ameliorate its side-effects, in particular, ifosfamide-induced encephalopathy (IIE). This has resulted in several candidates for the encephalopathic metabolite, including 2-chloroacetaldehyde, 2-chloroacetic acid, acrolein, 3-hydroxypropionic acid and S-carboxymethyl-L-cysteine. The pros and cons for each of these, together with other IFO metabolites, are discussed in detail. It is concluded that IFO produces encephalopathy in susceptible patients, but CP does not, by a "perfect storm," involving all of these five metabolites. Methylene blue (MB) administration appears to be generally effective in the prevention and treatment of IIE, in all probability by the inhibition of monoamine oxidase in brain potentiating serotonin levels that modulate the effects of IFO on GABAergic and glutamatergic systems. This review represents the authors' analysis of a large body of published research.
Collapse
|
|
31
|
Jin H, Wang L, Bernards R. Rational combinations of targeted cancer therapies: background, advances and challenges. Nat Rev Drug Discov 2023; 22:213-234. [PMID: 36509911 DOI: 10.1038/s41573-022-00615-z] [Citation(s) in RCA: 160] [Impact Index Per Article: 80.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/16/2022] [Indexed: 12/15/2022]
Abstract
Over the past two decades, elucidation of the genetic defects that underlie cancer has resulted in a plethora of novel targeted cancer drugs. Although these agents can initially be highly effective, resistance to single-agent therapies remains a major challenge. Combining drugs can help avoid resistance, but the number of possible drug combinations vastly exceeds what can be tested clinically, both financially and in terms of patient availability. Rational drug combinations based on a deep understanding of the underlying molecular mechanisms associated with therapy resistance are potentially powerful in the treatment of cancer. Here, we discuss the mechanisms of resistance to targeted therapies and how effective drug combinations can be identified to combat resistance. The challenges in clinically developing these combinations and future perspectives are considered.
Collapse
Affiliation(s)
- Haojie Jin
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Liqin Wang
- Division of Molecular Carcinogenesis, Oncode Institute, Netherlands Cancer Institute, Amsterdam, the Netherlands.
| | - René Bernards
- State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- Division of Molecular Carcinogenesis, Oncode Institute, Netherlands Cancer Institute, Amsterdam, the Netherlands.
| |
Collapse
|
|
32
|
Chemotherapy: how to reduce its adverse effects while maintaining the potency? Med Oncol 2023; 40:88. [PMID: 36735206 DOI: 10.1007/s12032-023-01954-6] [Citation(s) in RCA: 45] [Impact Index Per Article: 22.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2022] [Accepted: 01/18/2023] [Indexed: 02/04/2023]
Abstract
Chemotherapy is one of the widely used anticancer treatments that involves the use of powerful cytotoxic drugs to stop tumor growth by targeting rapidly dividing cells through various mechanisms, which will be elucidated in this review. Introduced during the early twentieth century, chemotherapy has since lengthened the longevity of innumerable cancer patients. However, the increase in lifespan is at the expense of quality of life as patients are at risk of developing short-term and long-term side effects following chemotherapy, such as alopecia (hair loss), chemotherapy-induced peripheral neuropathy, chemotherapy-induced nausea and vomiting, cardiotoxicity, diarrhea, infertility, and chemo brain. Currently, a number of these chemotherapy-induced adverse effects are managed through supportive care and approved treatments, while the rest of the side effects are unavoidable. Hence, chemotherapeutic drugs associated with inevitable side effects are only administered when their therapeutic role outweighs their chemotoxicity, thus severely limiting the potency of chemotherapy in treating malignancy. Therein, the potential approaches to alleviating side effects of chemotherapy ranging from pharmaceutical drugs to alternative therapies will be discussed in this review in hopes of increasing the tolerance and effectiveness of future chemotherapeutic treatments.
Collapse
|
|
33
|
Kim AW, Jaklitsch MT. The evolving landscape of thoracic surgical oncology. J Surg Oncol 2023; 127:217-220. [PMID: 36630095 PMCID: PMC10107667 DOI: 10.1002/jso.27174] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Accepted: 12/02/2022] [Indexed: 01/12/2023]
Abstract
The history of Thoracic Surgical Oncology warrants attribution to the strong foundational contributions of the past. Current surgical approaches and techniques along with newer systemic therapies are the product of iterative modifications to prior successes. Progress also fosters traditional thinking to be challenged and other classic topics to be revisited with a contemporary perspective. Cumulatively, past and present clinical and scientific efforts point toward a promising future in the evolving landscape of Thoracic Surgical Oncology.
Collapse
Affiliation(s)
- Anthony W Kim
- Division of Thoracic Surgery, Keck School of Medicine, University of Southern California, Los Angeles, California, USA
| | - Michael T Jaklitsch
- Division of Thoracic and Cardiac Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| |
Collapse
|
|
34
|
Guidolin V, Li Y, Jacobs FC, MacMillan ML, Villalta PW, Hecht SS, Balbo S. Characterization and quantitation of busulfan DNA adducts in the blood of patients receiving busulfan therapy. Mol Ther Oncolytics 2023; 28:197-210. [PMID: 36820303 PMCID: PMC9938526 DOI: 10.1016/j.omto.2023.01.005] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/14/2022] [Accepted: 01/18/2023] [Indexed: 01/22/2023] Open
Abstract
DNA alkylating drugs have been used as cancer chemotherapy with variable outcomes. The establishment of predictive biomarkers to identify patients who will effectively respond to treatment would allow for the development of personalized therapies. As the degree of interaction of alkylating drug with DNA plays a key role in their mechanism of action, our hypothesis is that the measurement of the DNA adducts formed by alkylating drugs could be used to inform patient stratification. Beginning with busulfan, we took advantage of our DNA adductomic approach to characterize DNA adducts formed by reacting busulfan with calf-thymus DNA. Samples collected from six patients undergoing busulfan-based chemotherapy prior to allogeneic hematopoietic cell transplantation were analyzed for the presence of busulfan-derived DNA adducts. Among the 15 adducts detected in vitro, 12 were observed in the patient blood confirming the presence of a large profile of DNA adducts in vivo. Two of the detected adducts were structurally confirmed by comparison with synthetic standards and quantified in patients. These data confirm our ability to comprehensively characterize busulfan-derived DNA damage and set the stage for the development of methods to support personalized chemotherapy.
Collapse
Affiliation(s)
- Valeria Guidolin
- Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA,School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA
| | - Yupeng Li
- Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA,Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA
| | - Foster C. Jacobs
- Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA,School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA
| | - Margaret L. MacMillan
- Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA,Blood and Marrow Transplantation & Cellular Therapy Program, Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455, USA
| | - Peter W. Villalta
- Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA,Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN 55455, USA
| | - Stephen S. Hecht
- Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA
| | - Silvia Balbo
- Masonic Cancer Center, University of Minnesota, Minneapolis, MN 55455, USA,School of Public Health, University of Minnesota, Minneapolis, MN 55455, USA,Corresponding author: Silvia Balbo, Masonic Cancer Center, University of Minnesota, 2231 6 Street SE - 2-145 CCRB, Minneapolis, MN 55455, USA.
| |
Collapse
|
|
35
|
Li R, Ren J, Zhang D, Lv M, Wang Z, Wang H, Zhang S, Du J, Jiang XD, Wang G. Attachment of −tBu groups to aza-BODIPY core at 3,5-sites with ultra-large Stokes shift to enhance photothermal therapy through apoptosis mechanism. Mater Today Bio 2022; 16:100446. [PMID: 36199559 PMCID: PMC9527945 DOI: 10.1016/j.mtbio.2022.100446] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 09/26/2022] [Accepted: 09/28/2022] [Indexed: 11/16/2022]
Abstract
By the introduction of the −tBu groups into aza-BODIPY core, di-tert-butyl-substituted aza-BODIPYs at 3,5-sites (tBuazaBDPs) were prepared for the first time. Based on the X-ray analysis of CN-tBuazaBDP, this molecular structure is twisted. Near-infrared dye SMe-tBuazaBDP has the ultra-large Stokes shift (152 nm) in aza-BODIPY system, combining with the twisted intramolecular charge transfer and the free rotation of the −tBu groups at 3,5-sites. Although the barrier-free rotors of the distal −tBu groups in SMe-tBuazaBDP result in low fluorescence quantum yield, the photothermal conversion efficiency is markedly enhanced. SMe-tBuazaBDP nanoparticles with low power laser irradiation were proven to block cancer cell cycle, inhibit cancer cell proliferation, and induce cancer cell apoptosis in photothermal therapy (PTT). The strategy of “direct attachment of −tBu groups to aza-BODIPY core” gives a new design platform for a photothermal therapy agent.
Di-tert-butyl-substituted aza-BODIPYs at 3,5-sites (tBuazaBDPs) were prepared for the first time. Near-infrared dye SMe-tBuazaBDP has the ultra-large Stokes shift (152 nm) in aza-BODIPY system. SMe-tBuazaBDP nanoparticles can photothermally induce apoptosis as a potential photothermal therapy agent.
Collapse
|
|
36
|
Levy M. Adequate trials: How the search for a cure shaped leukemia diagnosis. SOCIAL STUDIES OF SCIENCE 2022; 52:878-903. [PMID: 35946136 DOI: 10.1177/03063127221110137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
This article examines the relationship between diagnosis and therapy, focusing on the case of leukemia and cancer chemotherapy in the 1960s. This case, I argue, reinforces the need to study diagnoses from a social-science perspective, because the persistent controversy around leukemia classification was resolved by institutional restructuring introduced through clinical experimentation, rather than by techno-scientific advances. In an attempt to prove that chemical cancer therapy was possible, oncologists replaced the question 'Is this drug working?' with the question 'How can we make this drug work?' To create the conditions and criteria under which drugs could work, oncologists undertook the reclassification of cancers and patients, producing a new diagnostic style that reversed the roles of diagnosis and therapy. Experts gained and secured the power to classify not by solving existing problems, but by redefining what counts as a problem and what qualifies as a solution. Similarly, therapies can become transformative not only when they 'work', but when they work just well enough to mobilize resources and support. Theorizing these displacements, I develop the concept of 'adequate trials' in order to capture modes of innovation in which a deep commitment to give new technologies a 'fair chance' to succeed (i.e. an 'adequate trial') leads experts to redefine the tasks and goals of their field. To further our theoretical understanding of how rigid drug testing becomes malleable and conducive to normative change, I analyze the organizational, scientific, and jurisdictional conditions that gave rise to oncologists' practical orientations.
Collapse
|
|
37
|
Iqubal MK, Kaur H, Md S, Alhakamy NA, Iqubal A, Ali J, Baboota S. A technical note on emerging combination approach involved in the onconanotherapeutics. Drug Deliv 2022; 29:3197-3212. [PMID: 36226570 PMCID: PMC9578464 DOI: 10.1080/10717544.2022.2132018] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Cancer is the second cause of mortality worldwide, and the currently available conventional treatment approach is associated with serious side effects and poor clinical outcomes. Based on the outcome of the exploratory preclinical and clinical studies, it was found that therapeutic response increases multiple folds when anticancer drugs are used in combination. However, the conventional combination of anticancer drugs was associated with various limitations such as increased cost of treatment, systemic toxicity, drug resistance, and reduced pharmacokinetic attributes. Hence, attempts were made to formulate nanocarrier fabricated combinatorial drugs (NFCDs) to effectively manage and treat cancer. This approach offers several advantages, such as improved stability, lower drug exposure, targeted drug delivery, low side effects, and improved clinical outcome. Hence, in this review, first time, we have discussed the recent advancement and various types of nano carrier-based combinatorial drug delivery systems in a different type of cancer and highlighted the personalized combinatorial theranostic medicine as a futuristic anticancer treatment approach.
Collapse
Affiliation(s)
- Mohammad Kashif Iqubal
- Product Development Department, Sentiss Research Centre, Sentiss Pharma Pvt Ltd, Gurugram, India.,Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
| | - Harsimran Kaur
- Department of Pharmaceutics, Delhi Pharmaceutical Science and Research University, New Delhi, India
| | - Shadab Md
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Nabil A Alhakamy
- Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Ashif Iqubal
- Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
| | - Javed Ali
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
| | - Sanjula Baboota
- Department of Pharmaceutics, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, India
| |
Collapse
|
|
38
|
Mehkri Y, Woodford S, Pierre K, Dagra A, Hernandez J, Reza Hosseini Siyanaki M, Azab M, Lucke-Wold B. Focused Delivery of Chemotherapy to Augment Surgical Management of Brain Tumors. Curr Oncol 2022; 29:8846-8861. [PMID: 36421349 PMCID: PMC9689062 DOI: 10.3390/curroncol29110696] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Revised: 11/10/2022] [Accepted: 11/15/2022] [Indexed: 11/19/2022] Open
Abstract
Chemotherapy as an adjuvant therapy that has largely failed to significantly improve outcomes for aggressive brain tumors; some reasons include a weak blood brain barrier penetration and tumor heterogeneity. Recently, there has been interest in designing effective ways to deliver chemotherapy to the tumor. In this review, we discuss the mechanisms of focused chemotherapies that are currently under investigation. Nanoparticle delivery demonstrates both a superior permeability and retention. However, thus far, it has not demonstrated a therapeutic efficacy for brain tumors. Convection-enhanced delivery is an invasive, yet versatile method, which appears to have the greatest potential. Other vehicles, such as angiopep-2 decorated gold nanoparticles, polyamidoamine dendrimers, and lipid nanostructures have demonstrated efficacy through sustained release of focused chemotherapy and have either improved cell death or survival in humans or animal models. Finally, focused ultrasound is a safe and effective way to disrupt the blood brain barrier and augment other delivery methods. Clinical trials are currently underway to study the safety and efficacy of these methods in combination with standard of care.
Collapse
|
|
39
|
Donati G, Amati B. MYC and therapy resistance in cancer: risks and opportunities. Mol Oncol 2022; 16:3828-3854. [PMID: 36214609 PMCID: PMC9627787 DOI: 10.1002/1878-0261.13319] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 09/08/2022] [Accepted: 10/06/2022] [Indexed: 12/24/2022] Open
Abstract
The MYC transcription factor, encoded by the c-MYC proto-oncogene, is activated by growth-promoting signals, and is a key regulator of biosynthetic and metabolic pathways driving cell growth and proliferation. These same processes are deregulated in MYC-driven tumors, where they become critical for cancer cell proliferation and survival. As other oncogenic insults, overexpressed MYC induces a series of cellular stresses (metabolic, oxidative, replicative, etc.) collectively known as oncogenic stress, which impact not only on tumor progression, but also on the response to therapy, with profound, multifaceted consequences on clinical outcome. On one hand, recent evidence uncovered a widespread role for MYC in therapy resistance in multiple cancer types, with either standard chemotherapeutic or targeted regimens. Reciprocally, oncogenic MYC imparts a series of molecular and metabolic dependencies to cells, thus giving rise to cancer-specific vulnerabilities that may be exploited to obtain synthetic-lethal interactions with novel anticancer drugs. Here we will review the current knowledge on the links between MYC and therapeutic responses, and will discuss possible strategies to overcome resistance through new, targeted interventions.
Collapse
Affiliation(s)
- Giulio Donati
- European Institute of Oncology (IEO) – IRCCSMilanItaly
| | - Bruno Amati
- European Institute of Oncology (IEO) – IRCCSMilanItaly
| |
Collapse
|
|
40
|
Iron-Sulfur Clusters: A Key Factor of Regulated Cell Death in Cancer. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2022; 2022:7449941. [PMID: 36338346 PMCID: PMC9629928 DOI: 10.1155/2022/7449941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 09/23/2022] [Accepted: 10/07/2022] [Indexed: 11/21/2022]
Abstract
Iron-sulfur clusters are ancient cofactors that play crucial roles in myriad cellular functions. Recent studies have shown that iron-sulfur clusters are closely related to the mechanisms of multiple cell death modalities. In addition, numerous previous studies have demonstrated that iron-sulfur clusters play an important role in the development and treatment of cancer. This review first summarizes the close association of iron-sulfur clusters with cell death modalities such as ferroptosis, cuprotosis, PANoptosis, and apoptosis and their potential role in cancer activation and drug resistance. This review hopes to generate new cancer therapy ideas and overcome drug resistance by modulating iron-sulfur clusters.
Collapse
|
|
41
|
Mir SA, Hamid L, Bader GN, Shoaib A, Rahamathulla M, Alshahrani MY, Alam P, Shakeel F. Role of Nanotechnology in Overcoming the Multidrug Resistance in Cancer Therapy: A Review. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27196608. [PMID: 36235145 PMCID: PMC9571152 DOI: 10.3390/molecules27196608] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Revised: 09/29/2022] [Accepted: 10/02/2022] [Indexed: 11/06/2022]
Abstract
Cancer is one of the leading causes of morbidity and mortality around the globe and is likely to become the major cause of global death in the coming years. As per World Health Organization (WHO) report, every year there are over 10 and 9 million new cases and deaths from this disease. Chemotherapy, radiotherapy, and surgery are the three basic approaches to treating cancer. These approaches are aiming at eradicating all cancer cells with minimum off-target effects on other cell types. Most drugs have serious adverse effects due to the lack of target selectivity. On the other hand, resistance to already available drugs has emerged as a major obstacle in cancer chemotherapy, allowing cancer to proliferate irrespective of the chemotherapeutic agent. Consequently, it leads to multidrug resistance (MDR), a growing concern in the scientific community. To overcome this problem, in recent years, nanotechnology-based drug therapies have been explored and have shown great promise in overcoming resistance, with most nano-based drugs being explored at the clinical level. Through this review, we try to explain various mechanisms involved in multidrug resistance in cancer and the role nanotechnology has played in overcoming or reversing this resistance.
Collapse
Affiliation(s)
- Suhail Ahmad Mir
- Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal, Srinagar 190006, India
| | - Laraibah Hamid
- Department of Zoology, University of Kashmir, Hazratbal, Srinagar 190006, India
| | - Ghulam Nabi Bader
- Department of Pharmaceutical Sciences, University of Kashmir, Hazratbal, Srinagar 190006, India
| | - Ambreen Shoaib
- Department of Pharmacy Practice, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia
- Correspondence: (A.S.); (F.S.)
| | - Mohamed Rahamathulla
- Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 61421, Saudi Arabia
| | - Mohammad Y. Alshahrani
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha 61421, Saudi Arabia
| | - Prawez Alam
- Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
| | - Faiyaz Shakeel
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
- Correspondence: (A.S.); (F.S.)
| |
Collapse
|
|
42
|
Abstract
The nitrogen mustards are powerful cytotoxic and lymphoablative agents and have been used for more than 60 years. They are employed in the treatment of cancers, sarcomas, and hematologic malignancies. Cyclophosphamide, the most versatile of the nitrogen mustards, also has a place in stem cell transplantation and the therapy of autoimmune diseases. Adverse effects caused by the nitrogen mustards on the central nervous system, kidney, heart, bladder, and gonads remain important issues. Advances in analytical techniques have facilitated the investigation of the pharmacokinetics of the nitrogen mustards, especially the oxazaphosphorines, which are prodrugs requiring metabolic activation. Enzymes involved in the metabolism of cyclophosphamide and ifosfamide are very polymorphic, but a greater understanding of the pharmacogenomic influences on their activity has not yet translated into a personalized medicine approach. In addition to damaging DNA, the nitrogen mustards can act through other mechanisms, such as antiangiogenesis and immunomodulation. The immunomodulatory properties of cyclophosphamide are an area of current exploration. In particular, cyclophosphamide decreases the number and activity of regulatory T cells, and the interaction between cyclophosphamide and the intestinal microbiome is now recognized as an important factor. New derivatives of the nitrogen mustards continue to be assessed. Oxazaphosphorine analogs have been synthesized in attempts to both improve efficacy and reduce toxicity, with varying degrees of success. Combinations of the nitrogen mustards with monoclonal antibodies and small-molecule targeted agents are being evaluated. SIGNIFICANCE STATEMENT: The nitrogen mustards are important, well-established therapeutic agents that are used to treat a variety of diseases. Their role is continuing to evolve.
Collapse
Affiliation(s)
- Martin S Highley
- Plymouth Oncology Centre, Derriford Hospital, and Peninsula Medical School, University of Plymouth, Plymouth, United Kingdom (M.S.H.); Department of Animal Physiology and Neurobiology (B.L.) and Laboratory for Experimental Oncology (E.A.D.B.), University of Leuven, Leuven, Belgium; Oncology Department, University Hospital Antwerp, Edegem, Belgium (H.P.); and London Oncology Clinic, London, United Kingdom (P.G.H.)
| | - Bart Landuyt
- Plymouth Oncology Centre, Derriford Hospital, and Peninsula Medical School, University of Plymouth, Plymouth, United Kingdom (M.S.H.); Department of Animal Physiology and Neurobiology (B.L.) and Laboratory for Experimental Oncology (E.A.D.B.), University of Leuven, Leuven, Belgium; Oncology Department, University Hospital Antwerp, Edegem, Belgium (H.P.); and London Oncology Clinic, London, United Kingdom (P.G.H.)
| | - Hans Prenen
- Plymouth Oncology Centre, Derriford Hospital, and Peninsula Medical School, University of Plymouth, Plymouth, United Kingdom (M.S.H.); Department of Animal Physiology and Neurobiology (B.L.) and Laboratory for Experimental Oncology (E.A.D.B.), University of Leuven, Leuven, Belgium; Oncology Department, University Hospital Antwerp, Edegem, Belgium (H.P.); and London Oncology Clinic, London, United Kingdom (P.G.H.)
| | - Peter G Harper
- Plymouth Oncology Centre, Derriford Hospital, and Peninsula Medical School, University of Plymouth, Plymouth, United Kingdom (M.S.H.); Department of Animal Physiology and Neurobiology (B.L.) and Laboratory for Experimental Oncology (E.A.D.B.), University of Leuven, Leuven, Belgium; Oncology Department, University Hospital Antwerp, Edegem, Belgium (H.P.); and London Oncology Clinic, London, United Kingdom (P.G.H.)
| | - Ernst A De Bruijn
- Plymouth Oncology Centre, Derriford Hospital, and Peninsula Medical School, University of Plymouth, Plymouth, United Kingdom (M.S.H.); Department of Animal Physiology and Neurobiology (B.L.) and Laboratory for Experimental Oncology (E.A.D.B.), University of Leuven, Leuven, Belgium; Oncology Department, University Hospital Antwerp, Edegem, Belgium (H.P.); and London Oncology Clinic, London, United Kingdom (P.G.H.)
| |
Collapse
|
|
43
|
Emran TB, Shahriar A, Mahmud AR, Rahman T, Abir MH, Siddiquee MFR, Ahmed H, Rahman N, Nainu F, Wahyudin E, Mitra S, Dhama K, Habiballah MM, Haque S, Islam A, Hassan MM. Multidrug Resistance in Cancer: Understanding Molecular Mechanisms, Immunoprevention and Therapeutic Approaches. Front Oncol 2022; 12:891652. [PMID: 35814435 PMCID: PMC9262248 DOI: 10.3389/fonc.2022.891652] [Citation(s) in RCA: 209] [Impact Index Per Article: 69.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2022] [Accepted: 05/10/2022] [Indexed: 12/15/2022] Open
Abstract
Cancer is one of the leading causes of death worldwide. Several treatments are available for cancer treatment, but many treatment methods are ineffective against multidrug-resistant cancer. Multidrug resistance (MDR) represents a major obstacle to effective therapeutic interventions against cancer. This review describes the known MDR mechanisms in cancer cells and discusses ongoing laboratory approaches and novel therapeutic strategies that aim to inhibit, circumvent, or reverse MDR development in various cancer types. In this review, we discuss both intrinsic and acquired drug resistance, in addition to highlighting hypoxia- and autophagy-mediated drug resistance mechanisms. Several factors, including individual genetic differences, such as mutations, altered epigenetics, enhanced drug efflux, cell death inhibition, and various other molecular and cellular mechanisms, are responsible for the development of resistance against anticancer agents. Drug resistance can also depend on cellular autophagic and hypoxic status. The expression of drug-resistant genes and the regulatory mechanisms that determine drug resistance are also discussed. Methods to circumvent MDR, including immunoprevention, the use of microparticles and nanomedicine might result in better strategies for fighting cancer.
Collapse
Affiliation(s)
- Talha Bin Emran
- Department of Pharmacy, BGC Trust University Bangladesh, Chittagong, Bangladesh
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka, Bangladesh
| | - Asif Shahriar
- Department of Immunology and Microbiology, School of Medicine, University of Texas Rio Grande Valley, McAllen, TX, United States
| | - Aar Rafi Mahmud
- Department of Biochemistry and Molecular Biology, Mawlana Bhashani Science and Technology University, Tangail, Bangladesh
| | - Tanjilur Rahman
- Department of Biochemistry and Molecular Biology, Faculty of Biological Sciences, University of Chittagong, Chittagong, Bangladesh
| | - Mehedy Hasan Abir
- Faculty of Food Science and Technology, Chattogram Veterinary and Animal Sciences University, Chattogram, Bangladesh
| | | | - Hossain Ahmed
- Department of Biotechnology and Genetic Engineering, University of Development Alternative, Dhaka, Bangladesh
| | - Nova Rahman
- Department of Biochemistry and Molecular Biology, Jahangirnagar University, Dhaka, Bangladesh
| | - Firzan Nainu
- Department of Pharmacy, Faculty of Pharmacy, Hasanuddin University, Makassar, Indonesia
| | - Elly Wahyudin
- Department of Pharmacy, Faculty of Pharmacy, Hasanuddin University, Makassar, Indonesia
| | - Saikat Mitra
- Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
| | - Kuldeep Dhama
- Division of Pathology, ICAR-Indian Veterinary Research Institute, Bareilly, India
| | - Mahmoud M Habiballah
- Medical Laboratory Technology Department, Jazan University, Jazan, Saudi Arabia
- SMIRES for Consultation in Specialized Medical Laboratories, Jazan University, Jazan, Saudi Arabia
| | - Shafiul Haque
- Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Saudi Arabia
- Bursa Uludağ University Faculty of Medicine, Bursa, Turkey
| | | | - Mohammad Mahmudul Hassan
- Queensland Alliance for One Health Sciences, School of Veterinary Science, The University of Queensland, Gatton, QLD, Australia
- Department of Physiology, Biochemistry and Pharmacology, Faculty of Veterinary Medicine, Chattogram Veterinary and Animal Sciences University, Chattogram, Bangladesh
| |
Collapse
|
|
44
|
Rozsypal T, Kobliha Z. Identification of Nitrogen Mustard Chemical Warfare Agents in Sand by Gas Chromatography–Mass Spectrometry (GC-MS) in a Military Deployable Laboratory. ANAL LETT 2022. [DOI: 10.1080/00032719.2022.2081336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/01/2022]
Affiliation(s)
- Tomas Rozsypal
- Nuclear, Biological and Chemical Defence Institute, University of Defence, Vyskov, Czech Republic
| | - Zbynek Kobliha
- Nuclear, Biological and Chemical Defence Institute, University of Defence, Vyskov, Czech Republic
| |
Collapse
|
|
45
|
How CW, Teoh SL, Loh JS, Tan SLK, Foo JB, Ng HS, Wong SYW, Ong YS. Emerging Nanotheranostics for 5-Fluorouracil in Cancer Therapy: A Systematic Review on Efficacy, Safety, and Diagnostic Capability. Front Pharmacol 2022; 13:882704. [PMID: 35662688 PMCID: PMC9158334 DOI: 10.3389/fphar.2022.882704] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 04/07/2022] [Indexed: 11/13/2022] Open
Abstract
The conventional concept of using nanocarriers to deliver chemotherapeutic drugs has advanced to accommodate additional diagnostic capability. Nanotheranostic agents (NTA), combining both treatment and diagnostic tools, are an ideal example of engineering-health integration for cancer management. Owing to the diverse materials used to construct NTAs, their safety, effectiveness, and diagnostic accuracy could vary substantially. This systematic review consolidated current NTAs incorporating 5-fluorouracil and elucidated their toxicity, anticancer efficacy, and imaging capability. Medline and Embase databases were searched up to March 18, 2022. The search, selection, and extraction were performed by the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines to ensure completeness and reproducibility. Original research papers involving 5-fluorouracil in the preparation of nanoparticles which reported their efficacy, toxicity, and diagnostic capability in animal cancer models were recruited. The quality of included studies was assessed using the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies (CAMARADES) checklist. Nine studies were eligible for the systematic review. There was no significant toxicity reported based on animal weight and organ histology. Complete tumor remission was observed in several animal models using chemo-thermal ablation with NTAs, proving the enhancement of 5-fluorouracil efficacy. In terms of imaging performance, the time to achieve maximum tumor image intensity correlates with the presence of targeting ligand on NTAs. The NTAs, which are composed of tumor-targeting ligands, hold promises for further development. Based on the input of current NTA research on cancer, this review proposed a checklist of parameters to recommend researchers for their future NTA testing, especially in animal cancer studies. Systematic Review Registration: website, identifier registration number.
Collapse
Affiliation(s)
- Chee Wun How
- School of Pharmacy, Monash University Malaysia, Subang Jaya, Malaysia
| | - Siew Li Teoh
- School of Pharmacy, Monash University Malaysia, Subang Jaya, Malaysia
| | - Jian Sheng Loh
- School of Pharmacy, Monash University Malaysia, Subang Jaya, Malaysia
| | - Stella Li Kar Tan
- School of Pharmacy, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya, Malaysia
| | - Jhi Biau Foo
- School of Pharmacy, Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya, Malaysia
- Centre for Drug Discovery and Molecular Pharmacology (CDDMP), Faculty of Health and Medical Sciences, Taylor’s University, Subang Jaya, Malaysia
| | - Hui Suan Ng
- China-ASEAN College of Marine Sciences, Xiamen University Malaysia, Sepang, Malaysia
| | | | - Yong Sze Ong
- School of Pharmacy, Monash University Malaysia, Subang Jaya, Malaysia
| |
Collapse
|
|
46
|
Duan S, Buxton ILO. Evolution of Medical Approaches and Prominent Therapies in Breast Cancer. Cancers (Basel) 2022; 14:2450. [PMID: 35626053 PMCID: PMC9140094 DOI: 10.3390/cancers14102450] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2022] [Revised: 05/06/2022] [Accepted: 05/09/2022] [Indexed: 12/10/2022] Open
Abstract
An examination of the origins of medical approaches to breast cancer marks this disease as one of the most difficult to manage. As the early identification, diagnosis and treatment of breast cancer evolve, we will move to a time when each patient and their cancer can be assessed to determine unique patient-specific (personalized) approaches to therapy. Humans have attempted to manage breast cancer for millennia. Even today, the disease claims thousands of lives each year. In light of the increasingly sophisticated understanding of cancer diagnosis and treatment, together with our ultimate failure to offer a cure in the most difficult cases, it is instructive to reflect on the beginnings of our understanding.
Collapse
Affiliation(s)
- Suzann Duan
- Department of Pharmacology, University of Nevada, Reno School of Medicine, Reno, NV 89557, USA;
| | - Iain L. O. Buxton
- Department of Medicine, University of Arizona College of Medicine, Tucson, AZ 85724, USA
| |
Collapse
|
|
47
|
Miura K, Takahashi H, Nakagawa M, Hamada T, Uchino Y, Iizuka K, Ohtake S, Iriyama N, Hatta Y, Nakamura H. Ideal dose intensity of R-CHOP in diffuse large B-cell lymphoma. Expert Rev Anticancer Ther 2022; 22:583-595. [PMID: 35472312 DOI: 10.1080/14737140.2022.2071262] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION The standard of care for diffuse large B-cell lymphoma (DLBCL) is rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). However, its ideal dose intensity varies among cases. AREAS COVERED This review provides the latest insights on the dose intensity of R-CHOP for DLBCL patients. Specifically, we discussed the optimal dose intensity for elderly patients, the optimal number of treatment cycles for limited or advanced-stage diseases, and the role of dose-intensified therapies or adding targeted inhibitors. EXPERT OPINION Performing a comprehensive or simplified geriatric assessment can distinguish elderly DLBCL patients who will likely benefit from curative R-CHOP. Very elderly or medically unfit patients may need dose reduction in R-CHOP; the Age, Comorbidities, and Albumin index may aid decision-making. Four cycles of R-CHOP followed by two rituximab cycles comprise a new standard for low-risk, limited-stage DLBCL patients. Compared to eight cycles, six cycles of R-CHOP have similar efficacy and fewer toxicities for advanced-stage DLBCL. Dose-intensified therapy is not recommended in most DLBCL cases but may be considered for patients with double (or triple)-hit lymphoma. Applying targeted inhibitors and not merely escalating R-CHOP dose intensity through molecular subtyping will improve the treatment outcome for DLBCL.
Collapse
Affiliation(s)
- Katsuhiro Miura
- Tumor Center, Nihon University Itabashi Hospital (Director); 2Department of Hematology and Rheumatology, Nihon University School of Medicine (Associate Professor), Tokyo, Japan.,Department of Hematology and Rheumatology, Nihon University School of Medicine, Tokyo, Japan
| | - Hiromichi Takahashi
- Department of Hematology and Rheumatology, Nihon University School of Medicine, Tokyo, Japan.,Division of Laboratory Medicine, Department of Pathology and Microbiology, Nihon University School of Medicine (Assistant Professor), Tokyo, Japan
| | - Masaru Nakagawa
- Department of Hematology and Rheumatology, Nihon University School of Medicine, Tokyo, Japan.,Division of Laboratory Medicine, Department of Pathology and Microbiology, Nihon University School of Medicine (Assistant Professor), Tokyo, Japan
| | - Takashi Hamada
- Department of Hematology and Rheumatology, Nihon University School of Medicine, Tokyo, Japan
| | - Yoshihito Uchino
- Department of Hematology and Rheumatology, Nihon University School of Medicine, Tokyo, Japan
| | - Kazuhide Iizuka
- Department of Hematology and Rheumatology, Nihon University School of Medicine, Tokyo, Japan.,Division of Laboratory Medicine, Department of Pathology and Microbiology, Nihon University School of Medicine (Assistant Professor), Tokyo, Japan
| | - Shimon Ohtake
- Department of Hematology and Rheumatology, Nihon University School of Medicine, Tokyo, Japan
| | - Noriyoshi Iriyama
- Department of Hematology and Rheumatology, Nihon University School of Medicine, Tokyo, Japan
| | - Yoshihiro Hatta
- Department of Hematology and Rheumatology, Nihon University School of Medicine, Tokyo, Japan
| | - Hideki Nakamura
- Department of Hematology and Rheumatology, Nihon University School of Medicine, Tokyo, Japan
| |
Collapse
|
|
48
|
Rashid HM, Mahmod AI, Afifi FU, Talib WH. Antioxidant and Antiproliferation Activities of Lemon Verbena (Aloysia citrodora): An In Vitro and In Vivo Study. PLANTS 2022; 11:plants11060785. [PMID: 35336667 PMCID: PMC8951487 DOI: 10.3390/plants11060785] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/08/2022] [Revised: 03/09/2022] [Accepted: 03/12/2022] [Indexed: 02/07/2023]
Abstract
Aloysia citrodora (Verbenaceae) is traditionally used to treat various diseases, including bronchitis, insomnia, anxiety, digestive, and heart problems. In this study, this plant’s antioxidant and anti-proliferation effects were evaluated. In addition to volatiles extraction, different solvent extracts were prepared. The GC-MS, LC-MS analysis and the Foline-Ciocalteu (F-C) method were used to investigate the phytochemical components of the plant. MTT assay was used to measure the antiproliferative ability for each extract. Antioxidant activity was determined using the 2,2-diphenylpicrylhydrazyl (DPPH) assay. In in vivo anti-proliferation experiments, Balb/C mice were inoculated with tumor cells and IP-injected with ethyl acetate extract of A. citrodora. After treatment, a significant reduction in tumor size (57.97%) and undetected tumors (44.44%) were obtained in treated mice, demonstrating the antiproliferative efficacy of the ethyl acetate extract. Besides, ethanol extract revealed the most potent radical scavenging effect. The findings of this study displayed that A. citrodora has promising cytotoxic and antioxidant activities. Still, further testing is required to investigate the extract’s chemical composition to understand its mechanisms of action.
Collapse
Affiliation(s)
- Hasan M. Rashid
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan; (H.M.R.); (A.I.M.)
| | - Asma Ismail Mahmod
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan; (H.M.R.); (A.I.M.)
| | - Fatma U. Afifi
- Department of Pharmaceutical Chemistry and Pharmacognosy, Applied Science Private University, Amman 11931, Jordan; or
| | - Wamidh H. Talib
- Department of Clinical Pharmacy and Therapeutics, Applied Science Private University, Amman 11931, Jordan; (H.M.R.); (A.I.M.)
- Correspondence:
| |
Collapse
|
|
49
|
Investigation of interactions of doxorubicin with purine nucleobases by molecular modeling. J Mol Model 2022; 28:69. [PMID: 35218423 DOI: 10.1007/s00894-022-05031-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 01/18/2022] [Indexed: 10/19/2022]
Abstract
Doxorubicin, an anthracycline antibiotic with anti-tumor activity, is produced by the bacterium Streptomyces peucetius. The interactions between doxorubicin and genetic material and the details of the intercalation with DNA have been controversial issues. Thus, the interactions of doxorubicin with purine nucleobases were studied by quantum mechanical methods. Initially, conformer analyses of doxorubicin were performed with Spartan 08 software and 319 different conformers from 422 initial structures for doxorubicin were obtained. Geometry optimizations and frequency analyses were performed for each structure using density functional theory (DFT) at B3LYP/6-31G** level using Gaussian 09 software. The most stable 20 conformers of doxorubicin and tautomers of purine nucleobases were optimized again with ɷB97XD/6-31G** level and their interactions were also analyzed at the same level. The Discovery Studio 3.5 Visualizer was used to draw the initial and optimized structures of investigated geometries. The noncovalent interactions (NCIs) were visualized by calculating reduced density gradient (RDG) with Multiwfn program. The color-filled isosurfaces and RDG scatter maps of most stable interaction geometries were plotted by Visual Molecular Dynamics (VMD) software and Gnuplot 5.3 software, respectively. This study showed that adenine, guanine, and hypoxanthine nucleobases interact with doxorubicin by forming strong hydrogen bonds and π-π interactions. Considering the normal cellular conditions, the effect of solvent (water) on the interaction geometries were also analyzed and when compared to gas phase it was determined that the movements of the molecules were restricted and there was a minimal change between initial and optimized structures in the aqueous phase.
Collapse
|
|
50
|
Kulkarni R, Gupta S, Maheshwari A. Gynecologic Oncology: On the Shoulders of Giants. Indian J Med Paediatr Oncol 2022. [DOI: 10.1055/s-0042-1742658] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Abstract
AbstractGynecologic oncology is considered a new field, but its roots are buried deep in the past. As with other tumors, the earliest progress in modern times started with anesthesia and surgery. This was followed by landmark achievements in pathology, cytology, radiotherapy, chemotherapy, tumor virology, generation of high-quality evidence, and, more recently, genetics and genomics. Some of the most notable progresses in gynecologic cancers have been made by integrating the expertise of various specialties in multimodality management approaches. In this article we review the most important milestones in the history of gynecologic oncology and acknowledge the contributions of pioneers who made these possible.
Collapse
Affiliation(s)
- Rohini Kulkarni
- Department of Gynaecologic Oncology, Tata Memorial Centre and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Sudeep Gupta
- Department of Medical Oncology, Tata Memorial Centre and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| | - Amita Maheshwari
- Department of Gynaecologic Oncology, Tata Memorial Centre and Homi Bhabha National Institute, Mumbai, Maharashtra, India
| |
Collapse
|