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Wisniewski A, Humer D, Möller M, Kanje S, Spadiut O, Hober S. Targeted HER2-positive cancer therapy using ADAPT6 fused to horseradish peroxidase. N Biotechnol 2024; 83:74-81. [PMID: 39032630 DOI: 10.1016/j.nbt.2024.07.001] [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: 12/30/2023] [Revised: 07/05/2024] [Accepted: 07/17/2024] [Indexed: 07/23/2024]
Abstract
Targeted cancer therapy is a promising alternative to the currently established cancer treatments, aiming to selectively kill cancer cells while sparing healthy tissues. Hereby, molecular targeting agents, such as monoclonal antibodies, are used to bind to cancer cell surface markers specifically. Although these agents have shown great clinical success, limitations still remain such as low tumor penetration and off-target effects. To overcome this limitation, novel fusion proteins comprised of the two proteins ADAPT6 and Horseradish Peroxidase (HRP) were engineered. Cancer cell targeting is hereby enabled by the small scaffold protein ADAPT6, engineered to specifically bind to human epidermal growth factor receptor 2 (HER2), a cell surface marker overexpressed in various cancer types, while the enzyme HRP oxidizes the nontoxic prodrug indole-3-acetic acid (IAA) which leads to the formation of free radicals and thereby to cytotoxic effects on cancer cells. The high affinity to HER2, as well as the enzymatic activity of HRP, were still present for the ADAPT6-HRP fusion proteins. Further, in vitro cytotoxicity assay using HER2-positive SKOV-3 cells revealed a clear advantage of the fusion proteins over free HRP by association of the fusion proteins directly to the cancer cells and therefore sustained cell killing. This novel strategy of combining ADAPT6 and HRP represents a promising approach and a viable alternative to antibody conjugation for targeted cancer therapy.
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Affiliation(s)
- Andreas Wisniewski
- Department of Protein Science, KTH-Royal Institute of Technology, SE-10691 Stockholm, Sweden
| | - Diana Humer
- Institute of Chemical, Environmental and Bioscience Engineering, Research Area Biochemical Engineering, AT-1060 Vienna, Austria
| | - Marit Möller
- Department of Protein Science, KTH-Royal Institute of Technology, SE-10691 Stockholm, Sweden
| | - Sara Kanje
- Department of Protein Science, KTH-Royal Institute of Technology, SE-10691 Stockholm, Sweden
| | - Oliver Spadiut
- Institute of Chemical, Environmental and Bioscience Engineering, Research Area Biochemical Engineering, AT-1060 Vienna, Austria
| | - Sophia Hober
- Department of Protein Science, KTH-Royal Institute of Technology, SE-10691 Stockholm, Sweden.
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2
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Nassir R, Esheba G. Implementation of Next-Generation Sequencing in Saudi Arabia for HER2-Positive Breast Cancer. Saudi J Biol Sci 2022; 29:1808-1812. [PMID: 35280536 PMCID: PMC8913378 DOI: 10.1016/j.sjbs.2021.10.044] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 10/14/2021] [Accepted: 10/16/2021] [Indexed: 11/25/2022] Open
Abstract
Breast cancer is a common malignancy that poses a hazard to women's health. In 2021, around 2.3 million new cases are predicted to be discovered, with a mortality rate of 6.9% on average. Breast cancer accounts for 14.8% of malignancies among the Saudis with an 8.5% fatality rate. Breast cancers that are HER2 positive account for 15 to 20% of all breast cancers. We intended to investigate the genetic mutations and the clinicopathological aspects of HER2 positive breast cancer patients. We used TruSight Tumor 15 using Next-Generation Sequencing (NGS) to look at genetic changes in 126 Saudi women with stage I to IV breast cancer. c-MET (p = 0.001), c-KIT (p = 0.001), and PIK3CA (p = 0.0001), were shown to be substantially linked with HER2 positive patients. We also detected mutations in other genes, including BRAF, EGFR, and KRAS. Tumor size, grade, stage, and nodal status were all associated with increased levels of HER2 expression. Our results recommend that patients with HER2 positive breast cancer in Saudi Arabia have a high mutational burden, which may be related to trastuzumab resistance. We expect that in the future, targeting these mutations will be a promising therapeutic method for the treatment of breast cancer.
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Affiliation(s)
- Rami Nassir
- Department of Pathology, School of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Ghada Esheba
- Department of Pathology, School of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia
- Department of Pathology, Faculty of Medicine, Tanta University, Egypt
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3
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Gumusay O, Vitiello PP, Wabl C, Corcoran RB, Bardelli A, Rugo HS. Strategic Combinations to Prevent and Overcome Resistance to Targeted Therapies in Oncology. Am Soc Clin Oncol Educ Book 2020; 40:e292-e308. [PMID: 32453634 DOI: 10.1200/edbk_280845] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Recent advances in the understanding of underlying molecular signaling mechanisms of cancer susceptibility and progression have led to an increase in the use of targeted therapies for cancer treatment. Despite improvements in survival with new treatment options in oncology, resistance to therapy is a major obstacle to the long-term effectiveness of targeted agents in metastatic cancer treatment, culminating in insensitivity to treatment and tumor outgrowth. Adaptive resistance can play an important role in primary and upfront resistance to therapy as well as in secondary or acquired resistance. By focusing on colorectal and breast tumors, we discuss how therapeutic combinations based on specific drivers of tumor biology can be used to overcome resistance. We present how monitoring tumor dynamics over time may allow early adaptation of treatment. Breast cancer is the most common malignancy in women worldwide, and the majority of these cancers are sensitive to endocrine therapy (ET) blocking the production of or response to estrogen. However, primary and acquired resistance limits efficacy. Recent combinations of agents targeted to pathways that drive tumor growth resistance with ET have resulted in remarkable improvements in disease response and control, improving survival in some settings. In this review, we summarize adaptive resistance mechanisms, approaches to combination strategies, and dynamic tumor monitoring to improve efficacy and overcome resistance. We provide examples of combination therapy to enhance the efficacy of targeted therapies in breast and colorectal tumors.
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Affiliation(s)
- Ozge Gumusay
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.,Department of Internal Medicine, Division of Medical Oncology, Gaziosmanpasa University Faculty of Medicine, Tokat, Turkey
| | - Pietro Paolo Vitiello
- Department of Oncology, University of Torino, Candiolo (TO), Italy.,Dipartimento di Medicina di Precisione, Unità di Oncologia Medica, Università degli Studi della Campania Luigi Vanvitelli, Italy
| | - Chiara Wabl
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA
| | | | - Alberto Bardelli
- Department of Oncology, University of Torino, Candiolo (TO), Italy.,Candiolo Cancer Institute, Candiolo (TO), Italy
| | - Hope S Rugo
- UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA
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Dankó D, Blay JY, Garrison LP. Challenges in the value assessment, pricing and funding of targeted combination therapies in oncology. Health Policy 2019; 123:1230-1236. [PMID: 31337514 DOI: 10.1016/j.healthpol.2019.07.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2018] [Revised: 04/24/2019] [Accepted: 07/10/2019] [Indexed: 01/07/2023]
Abstract
BACKGROUND The use of targeted combination therapy (TCT) is becoming the standard of care in oncology as cancers are attacked through multiple inhibition mechanisms. TCTs pose a budget challenge to health systems and an economic return challenge for companies developing them. METHODS We conducted a systematic literature review to identify challenges specific to TCTs and reviewed publicly available reports by health technology assessment and pricing and reimbursement bodies. We synthesized our findings into a problem map. RESULTS AND DISCUSSION Challenges and policy solutions linked to TCTs remain almost fully unexplored; we identified few resources that explicitly addressed TCTs. Contributors to the budget challenge are found at different layers; they and include static willingness-to-pay (WTP) for TCTs and inefficiencies in managing prices of backbone therapies. Economic return challenges are related to payer-imposed restrictions, peculiarities of TCT development, and conflicting incentives of pharmaceutical companies that own constituent therapies. Consequences are delayed or restricted patient access to TCTs, disincentives for research and development, and fewer life years gained. CONCLUSIONS Multiple issues will lead to the unsustainability of funding systems and possible conflict between stakeholders around access to TCTs. To manage these, new value assessment and attribution methodologies, modified trial designs and differentiated WTP thresholds can be considered in ways that are customized to the characteristics of different health systems.
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Affiliation(s)
- D Dankó
- Ideas & Solutions, Kelenhegyi út 16B, 1118 Budapest, Hungary.
| | - J-Y Blay
- Centre Léon Bérard, Lyon, France
| | - L P Garrison
- University of Washington, Department of Pharmacy, Seattle (WA), United States
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5
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A modified DAW-22 compound F-B1 inhibits Bcr/Abl and induces apoptosis in chronic myelogenous leukemia cells. Anticancer Drugs 2018; 30:159-166. [PMID: 30422832 DOI: 10.1097/cad.0000000000000712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The Bcr/Abl kinase is an oncogenic fusion protein that plays a central role in the pathogenesis of chronic myeloid leukemia (CML). Some small-molecule kinase inhibitors such as imatinib were developed in the treatment of CML; however, resistant to imatinib is an emerging problem of CML therapy. Hence, additional approaches or compounds targeting leukemogenic cells are required. F-B1 is a new compound obtained by modifying DAW-22, a natural sesquiterpenoid coumarin, which was isolated from traditional Chinese medicine Ferula ferulaeoides (Steud.) Korov. F-B1 was found to inhibit the growth of myelogenous leukemia cell lines, that is, K562 cells bearing wild-type Bcr/Abl and imatinib-resistant K562G cells. F-B1 potently down-regulated the mRNA and protein levels of Bcr/Abl, followed by suppression of the downstream molecules such as Akt, externally regulated kinases, and nuclear factor κB. In addition, F-B1 also induced cell apoptosis by impairing the balance between proapoptotic protein Bax and antiapoptotic proteins Bcl-2 and Bcl-XL and increased the activity of mitochondrial-dependent apoptosis in nude mouse xenografts. Experimental validation results together demonstrated that F-B1 can inhibit Bcr/Abl fusion proteins in K562 and K562G cells, implying that F-B1 might be a promising drug to treat CML, especially the imatinib-resistant CML.
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Xu J, Sun T, Guo X, Wang Y, Jing M. Estrogen receptor-α promoter methylation is a biomarker for outcome prediction of cisplatin resistance in triple-negative breast cancer. Oncol Lett 2017; 15:2855-2862. [PMID: 29456719 PMCID: PMC5778783 DOI: 10.3892/ol.2017.7637] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2015] [Accepted: 11/02/2017] [Indexed: 12/20/2022] Open
Abstract
A number of previous studies have indicated the presence of a link between estrogen receptor-α (ERα) methylation and triple-negative breast cancer (TNBC). However, the association between ERα methylation and drug resistance during the treatment of TNBC remains unclear. Methylation-specific polymerase chain reaction was used to investigate the methylation of ERα in the genomic DNA of 35 patients with TNBC who were defined as cisplatin-based chemotherapy-resistant using chemosensitivity testing. Survival probabilities by covariates were assessed using Kaplan-Meier estimator survival analysis and Cox's proportional hazards models, adjusting for age, menopausal status, tumor size, lymph node metastasis and ERα promoter DNA methylation. Of the 35 patients with TNBC analyzed, 8 exhibited ERα promoter DNA methylation. Cisplatin resistance was confirmed to be overwhelmingly associated with ERα methylation by univariate and multivariate analysis. Even in a limited analysis in patients with ERα methylation, the results generated from methylated tumor tissue and unmethylated tumor tissue revealed that expression of breast cancer type 1/2 susceptibility proteins was increased in ERα-methylated breast tumor tissue compared with in unmethylated tissue. The ERα methylation group tended to have significantly shorter progression-free (P=0.010) and overall (P=0.023) survival times compared with those in the unmethylated group. Similarly, shorter progression-free (P=0.024) and overall (P=0.018) survival times were observed in the cisplatin-resistant group compared with the cisplatin-non-resistant group. ERα methylation predicts a poor clinical outcome for patients with TNBC. The results of the present study indicated that ERα methylation may be a candidate surrogate biomarker for outcome prediction and cisplatin resistance in TNBC. Further investigation is required to identify potential biomarkers in a larger cohort in a prospective study.
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Affiliation(s)
- Junnan Xu
- Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China
| | - Tao Sun
- Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China
| | - Xiangyu Guo
- Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China
| | - Yan Wang
- Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China
| | - Mingxi Jing
- Department of Medical Oncology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning 110042, P.R. China
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Atkinson TM, Rodríguez VM, Gordon M, Avildsen IK, Emanu JC, Jewell ST, Anselmi KA, Ginex PK. The Association Between Patient-Reported and Objective Oral Anticancer Medication Adherence Measures: A Systematic Review
. Oncol Nurs Forum 2017; 43:576-82. [PMID: 27541550 DOI: 10.1188/16.onf.576-582] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
PROBLEM IDENTIFICATION Oral anticancer medication (OAM) use has been steadily increasing, leading to several patient benefits. A notable challenge for nurses is accurate monitoring of patient OAM regimens because nonadherence is associated with poor health outcomes and decreased survival. Currently, no gold standard measure of OAM adherence exists. The authors conducted a systematic review of the association between objective and patient-reported measures of OAM adherence.
. LITERATURE SEARCH A systematic electronic literature search was conducted using PubMed, EMBASE, Scopus, PsycINFO®, Cochrane Library, Web of Science, and CINAHL® databases through November 2014.
. DATA EVALUATION Articles were independently reviewed to determine whether they included an original characterization of the level of association between objective and patient-reported measures of OAM adherence.
. SYNTHESIS From a total of 11,135 articles retrieved, eight studies met inclusion criteria. Objective adherence was primarily assessed using pill counts or Medication Event Monitoring System (MEMSCap™). Patient-reported adherence was most commonly assessed using study-specific questionnaires. Significant positive correlations were observed between objective and patient-reported adherence across most studies, with three studies reporting higher rates of adherence via patient reporting.
. CONCLUSIONS Despite variation in the OAMs and measures used, patient-reported adherence rates were equal to or higher than objective adherence measures across studies. Social desirability bias may be a concern; however, given the significant concordance observed, using patient-reported methods in future studies of OAM adherence may be justified.
. IMPLICATIONS FOR NURSING This review provides evidence to support nursing use of patient-reported measures to accurately monitor OAM adherence and potentially improve the quality of patient-provider communication.
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8
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Kamel HFM, Al-Amodi HSAB. Exploitation of Gene Expression and Cancer Biomarkers in Paving the Path to Era of Personalized Medicine. GENOMICS PROTEOMICS & BIOINFORMATICS 2017; 15:220-235. [PMID: 28813639 PMCID: PMC5582794 DOI: 10.1016/j.gpb.2016.11.005] [Citation(s) in RCA: 72] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Revised: 10/29/2016] [Accepted: 11/11/2016] [Indexed: 02/06/2023]
Abstract
Cancer therapy agents have been used extensively as cytotoxic drugs against tissue or organ of a specific type of cancer. With the better understanding of molecular mechanisms underlying carcinogenesis and cellular events during cancer progression and metastasis, it is now possible to use targeted therapy for these molecular events. Targeted therapy is able to identify cancer patients with dissimilar genetic defects at cellular level for the same cancer type and consequently requires individualized approach for treatment. Cancer therapy begins to shift steadily from the traditional approach of “one regimen for all patients” to a more individualized approach, through which each patient will be treated specifically according to their specific genetic defects. Personalized medicine accordingly requires identification of indicators or markers that guide in the decision making of such therapy to the chosen patients for more effective therapy. Cancer biomarkers are frequently used in clinical practice for diagnosis and prognosis, as well as identification of responsive patients and prediction of treatment response of cancer patient. The rapid breakthrough and development of microarray and sequencing technologies is probably the main tool for paving the way toward “individualized biomarker-driven cancer therapy” or “personalized medicine”. In this review, we aim to provide an updated knowledge and overview of the current landscape of cancer biomarkers and their role in personalized medicine, emphasizing the impact of genomics on the implementation of new potential targeted therapies and development of novel cancer biomarkers in improving the outcome of cancer therapy.
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Affiliation(s)
- Hala Fawzy Mohamed Kamel
- Biochemistry Department, Faculty of Medicine, Umm AL-Qura University, Makhha 21955, Saudi Arabia; Medical Biochemistry Department, Faculty of Medicine, Ain Shams University, Cairo 11566, Egypt.
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Spoelstra SL, Sansoucie H. Putting evidence into practice: evidence-based interventions for oral agents for cancer. Clin J Oncol Nurs 2017; 19:60-72. [PMID: 26030394 DOI: 10.1188/15.s1.cjon.60-72] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
BACKGROUND The limited evidence available suggests that adherence to oral agents for cancer is a significant clinical problem and may have a substantial impact on treatment success or failure. Adherence is a difficult issue among patients who are very sick with a life-threatening disease who often must adhere to complex treatment protocols independently at home. OBJECTIVES This article aims to identify effective interventions for the promotion, treatment, and management of adherence to oral agents for cancer and to synthesize the literature for use in clinical practice. METHODS As part of the Oncology Nursing Society (ONS) Putting Evidence Into Practice (PEP) initiative, a comprehensive examination of the current literature was conducted to identify effective interventions for patients prescribed oral agents for cancer. The ONS PEP weight-of-evidence classification schema levels of evidence were used to categorize interventions to assist nurses in identifying strategies that are effective at improving adherence. FINDINGS The majority of evidence found was conducted in conditions other than cancer; therefore, research is needed to identify whether these interventions are effective at promoting adherence in patients with cancer.
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10
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Leung LKS, Mok K, Liu C, Chan SL. What do oncologists need to know about biosimilar products? CHINESE JOURNAL OF CANCER 2016; 35:91. [PMID: 27733189 PMCID: PMC5062853 DOI: 10.1186/s40880-016-0151-x] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/24/2015] [Accepted: 08/29/2016] [Indexed: 11/25/2022]
Abstract
Many biologic products have improved the outcomes of cancer patients, but the costs can substantially burden healthcare systems. Biosimilar products can potentially reduce drug costs and increase patient access to beneficial treatments. Approval of a biosimilar product relies on the demonstration of "comparability" or "no clinically meaningful differences" as compared to its reference biologic product. Biosimilar products for erythropoietin, granulocyte colony-stimulating factor, trastuzumab, and rituximab are already available, and the regulatory processes in various countries are constantly evolving. It is important that oncologists be familiar with the potential issues surrounding the clinical use of biosimilar products. In this review article, we provide background information about biosimilar products and their regulatory approval processes, followed by a discussion of individual biosimilar drugs.
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Affiliation(s)
- Linda K. S. Leung
- State Key Laboratory in Oncology in South China, Department of Clinical Oncology, Sir YK Pao Center for Cancer, Hong Kong Cancer Institute and Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Kevin Mok
- Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Calvin Liu
- Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China
| | - Stephen L. Chan
- State Key Laboratory in Oncology in South China, Department of Clinical Oncology, Sir YK Pao Center for Cancer, Hong Kong Cancer Institute and Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
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Spoelstra S, Given C, Sikorskii A, Coursaris C, Majumder A, DeKoekkoek T, Schueller M, Given B. Feasibility of a Text Messaging Intervention to Promote Self-Management for Patients Prescribed Oral Anticancer Agents. Oncol Nurs Forum 2015; 42:647-57. [DOI: 10.1188/15.onf.647-657] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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Gribben JG, Fowler N, Morschhauser F. Mechanisms of Action of Lenalidomide in B-Cell Non-Hodgkin Lymphoma. J Clin Oncol 2015; 33:2803-11. [PMID: 26195701 PMCID: PMC5320950 DOI: 10.1200/jco.2014.59.5363] [Citation(s) in RCA: 235] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022] Open
Abstract
Lenalidomide is an orally active immunomodulatory drug that has direct antineoplastic activity and indirect effects mediated through multiple types of immune cells found in the tumor microenvironment, including B, T, natural killer (NK), and dendritic cells. Recently, the E3 ubiquitin ligase cereblon was identified as a molecular target that may underlie the effects of lenalidomide on tumor cells, as well as on cells in the tumor microenvironment. Decreases in cereblon attenuate these effects and also confer resistance to lenalidomide. Tumoricidal effects of lenalidomide are associated with reduced interferon regulatory factor 4, a downstream target of cereblon. Lenalidomide stimulates proliferation and activation of NK cells, thereby enhancing NK cell-mediated cytotoxicity and antibody-dependent cellular cytotoxicity. These effects appear to be secondary to cytokine production from T cells. Lenalidomide has been shown to produce synergistic effects in experimental models when evaluated in combination with rituximab, dexamethasone, bortezomib, and B-cell receptor signaling inhibitors, consistent with mechanisms complementary to these agents. These experimental findings have translated to the clinic, where single-agent use displays durable responses in relapsed/refractory non-Hodgkin lymphoma, and combination with rituximab and other agents leads to improved responses at first line and in relapsed/refractory disease. The activity of lenalidomide is evident across multiple lymphoma subtypes, including indolent and aggressive forms. The interaction among cell types in the immune microenvironment is increasingly recognized as important to tumor cell recognition and destruction, as well as to protection of normal immune cells, as reflected by lenalidomide studies across multiple types of B-cell lymphomas.
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Affiliation(s)
- John G Gribben
- John G. Gribben, Barts Cancer Institute, London, United Kingdom; Nathan Fowler, The University of Texas MD Anderson Cancer Center, Houston, TX; and Franck Morschhauser, Centre Hospitalier Universitaire Régional de Lille, Unité Groupe de Recherche sur les formes Injectables et les Technologies Associées, Lille, France.
| | - Nathan Fowler
- John G. Gribben, Barts Cancer Institute, London, United Kingdom; Nathan Fowler, The University of Texas MD Anderson Cancer Center, Houston, TX; and Franck Morschhauser, Centre Hospitalier Universitaire Régional de Lille, Unité Groupe de Recherche sur les formes Injectables et les Technologies Associées, Lille, France
| | - Franck Morschhauser
- John G. Gribben, Barts Cancer Institute, London, United Kingdom; Nathan Fowler, The University of Texas MD Anderson Cancer Center, Houston, TX; and Franck Morschhauser, Centre Hospitalier Universitaire Régional de Lille, Unité Groupe de Recherche sur les formes Injectables et les Technologies Associées, Lille, France
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13
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Spoelstra SL, Given CW, Sikorskii A, Majumder A, Schueller M, Given BA. Treatment with oral anticancer agents: symptom severity and attribution, and interference with comorbidity management. Oncol Nurs Forum 2015; 42:80-8. [PMID: 25490974 DOI: 10.1188/15.onf.42-01p] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
PURPOSE/OBJECTIVES To evaluate the prevalence, severity, and attribution of symptoms, as well as the interference with management of comorbidities, in patients who have been prescribed oral anticancer agents (OAs). DESIGN Descriptive exploratory study. SETTING A comprehensive cancer center and two community-based oncology programs in the midwestern United States. SAMPLE 30 adults undergoing OA treatment. METHODS Five phone interviews were conducted during eight weeks. Linear mixed effects and generalized estimating equations were used to examine symptoms and interference over time. MAIN RESEARCH VARIABLES Symptoms and comorbid conditions. FINDINGS The mean age of participants was 65.1 years. Fifteen participants were female, 25 were Caucasian, and 23 had comorbidities. Twenty-one patients had late-stage cancer, and rates of adherence were 90%. Fatigue, sleep disturbance, and numbness or tingling in hands and feet were highly prevalent symptoms. Younger age was associated with higher symptom severity (p < 0.01) and interference (p = 0.01). Patients with more comorbidities tended to report higher symptom severity. Simultaneous IV chemotherapy was not a predictor of symptom severity or interference over age and comorbidity. Symptoms were most frequently attributed to cancer and its treatment. Patients with a greater number of comorbidities were more likely to include comorbidities in symptom attribution and reported interference from the OA with managing comorbid conditions. CONCLUSIONS Symptoms may be more severe in patients prescribed OAs who are younger and have comorbid conditions. More comorbidities and absence of simultaneous IV chemotherapy increased the likelihood of inclusion of chronic conditions in symptom attribution. Patients reported that OA treatment interfered with comorbidity management. IMPLICATIONS FOR NURSING Nurses need to take comorbidities into account when caring for patients prescribed OAs because the chronic conditions may influence symptom severity and the ability to manage symptoms.
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Affiliation(s)
| | - Charles W Given
- Department of Family Medicine, Michigan State University in East Lansing
| | - Alla Sikorskii
- Department of Statistics and Probability, Michigan State University in East Lansing
| | - Atreyee Majumder
- Department of Statistics and Probability, Michigan State University in East Lansing
| | | | - Barbara A Given
- College of Nursing, Michigan State University in East Lansing
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14
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Spoelstra SL, Given CW, Sikorskii A, Coursaris CK, Majumder A, DeKoekkoek T, Schueller M, Given BA. A randomized controlled trial of the feasibility and preliminary efficacy of a texting intervention on medication adherence in adults prescribed oral anti-cancer agents: study protocol. J Adv Nurs 2015; 71:2965-76. [PMID: 26100719 DOI: 10.1111/jan.12714] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/26/2015] [Indexed: 11/27/2022]
Abstract
AIM The aim of this study was to report a study protocol that examines feasibility, preliminary efficacy and satisfaction of a text message intervention on the outcome of medication adherence in adult patients prescribed oral anti-cancer agents. BACKGROUND Administration of oral anti-cancer agents occurs in the home setting, requiring patients to self-manage the regimen as prescribed. However, many barriers to medication adherence exist: regimens are often complex, with cycling of two or more medications; side effects of treatment; most cancer patients are older with comorbid conditions and competing demands; and cognitive decline and forgetfulness may occur. Research indicates patients miss nearly one-third of the prescribed oral anti-cancer agent dosages. Text message interventions have been shown to improve medication adherence in chronic conditions other than cancer. However, a majority of those patients were less than 50 years of age and most cancer patients are diagnosed later in life. DESIGN A two-group randomized controlled trial with repeated measures. METHODS Seventy-five adult patients newly prescribed an oral anti-cancer agent will be recruited (project funded in April 2013) from community cancer centres and a specialty pharmacy. Participants will be randomized to either a control group (n = 25; usual care) or an intervention group (n = 50; usual care plus text messages timed to medication regimen). Outcome measures include: medication adherence, feasibility and satisfaction with the intervention. Data will be collected over 8 weeks: baseline, weekly and exit. DISCUSSION Standardized text message intervention protocol and detailed study procedures have been developed in this study to improve medication adherence.
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Affiliation(s)
- Sandra L Spoelstra
- College of Nursing, Michigan State University, East Lansing, Michigan, USA
| | - Charles W Given
- Institute for Health Care Studies, Michigan State University, East Lansing, Michigan, USA
| | - Alla Sikorskii
- Department of Statistics and Probability, Michigan State University, East Lansing, Michigan, USA
| | - Constantinos K Coursaris
- Department of Telecommunication, Information Studies (Dr. Coursaris), Michigan State University, East Lansing, Michigan, USA
| | - Atreyee Majumder
- Department of Statistics and Probability, Michigan State University, East Lansing, Michigan, USA
| | - Tracy DeKoekkoek
- College of Nursing, Michigan State University, East Lansing, Michigan, USA
| | - Monica Schueller
- College of Nursing, Michigan State University, East Lansing, Michigan, USA
| | - Barbara A Given
- College of Nursing, Michigan State University, East Lansing, Michigan, USA
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15
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Spoelstra S. Why Patients Prescribed Oral Agents for Cancer Need Training: A Case Study. Clin J Oncol Nurs 2015; 19:3-5. [DOI: 10.1188/15.s1.cjon.3-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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16
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Teo T, Yu M, Yang Y, Gillam T, Lam F, Sykes MJ, Wang S. Pharmacologic co-inhibition of Mnks and mTORC1 synergistically suppresses proliferation and perturbs cell cycle progression in blast crisis-chronic myeloid leukemia cells. Cancer Lett 2015; 357:612-23. [DOI: 10.1016/j.canlet.2014.12.029] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2014] [Revised: 12/11/2014] [Accepted: 12/11/2014] [Indexed: 01/03/2023]
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17
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Guo B, Li Y. Bayesian dose-finding designs for combination of molecularly targeted agents assuming partial stochastic ordering. Stat Med 2014; 34:859-75. [PMID: 25413162 PMCID: PMC4359011 DOI: 10.1002/sim.6376] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2014] [Revised: 09/30/2014] [Accepted: 11/01/2014] [Indexed: 12/04/2022]
Abstract
Molecularly targeted agent (MTA) combination therapy is in the early stages of development. When using a fixed dose of one agent in combinations of MTAs, toxicity and efficacy do not necessarily increase with an increasing dose of the other agent. Thus, in dose-finding trials for combinations of MTAs, interest may lie in identifying the optimal biological dose combinations (OBDCs), defined as the lowest dose combinations (in a certain sense) that are safe and have the highest efficacy level meeting a prespecified target. The limited existing designs for these trials use parametric dose–efficacy and dose–toxicity models. Motivated by a phase I/II clinical trial of a combination of two MTAs in patients with pancreatic, endometrial, or colorectal cancer, we propose Bayesian dose-finding designs to identify the OBDCs without parametric model assumptions. The proposed approach is based only on partial stochastic ordering assumptions for the effects of the combined MTAs and uses isotonic regression to estimate partially stochastically ordered marginal posterior distributions of the efficacy and toxicity probabilities. We demonstrate that our proposed method appropriately accounts for the partial ordering constraints, including potential plateaus on the dose–response surfaces, and is computationally efficient. We develop a dose-combination-finding algorithm to identify the OBDCs. We use simulations to compare the proposed designs with an alternative design based on Bayesian isotonic regression transformation and a design based on parametric change-point dose–toxicity and dose–efficacy models and demonstrate desirable operating characteristics of the proposed designs. © 2014 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.
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Affiliation(s)
- Beibei Guo
- Department of Experimental Statistics, Louisiana State University, Baton Rouge, LA, 70803, U.S.A
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18
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Idée JM, Fretellier N, Robic C, Corot C. The role of gadolinium chelates in the mechanism of nephrogenic systemic fibrosis: A critical update. Crit Rev Toxicol 2014; 44:895-913. [PMID: 25257840 DOI: 10.3109/10408444.2014.955568] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Affiliation(s)
- Jean-Marc Idée
- Guerbet, Research & Innovation Division , Aulnay-sous-Bois , France
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19
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Teng CLJ, Han SM, Wu WC, Hsueh CM, Tsai JR, Hwang WL, Hsu SL. Mechanistic aspects of lauryl gallate-induced differentiation and apoptosis in human acute myeloid leukemia cells. Food Chem Toxicol 2014; 71:197-206. [DOI: 10.1016/j.fct.2014.06.019] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2013] [Revised: 06/12/2014] [Accepted: 06/23/2014] [Indexed: 11/29/2022]
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Casey SC, Li Y, Fan AC, Felsher DW. Oncogene withdrawal engages the immune system to induce sustained cancer regression. J Immunother Cancer 2014; 2:24. [PMID: 25089198 PMCID: PMC4118610 DOI: 10.1186/2051-1426-2-24] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2014] [Accepted: 06/06/2014] [Indexed: 02/06/2023] Open
Abstract
The targeted inactivation of a single oncogene can induce dramatic tumor regression, suggesting that cancers are “oncogene addicted.” Tumor regression following oncogene inactivation has been thought to be a consequence of restoration of normal physiological programs that induce proliferative arrest, apoptosis, differentiation, and cellular senescence. However, recent observations illustrate that oncogene addiction is highly dependent upon the host immune cells. In particular, CD4+ helper T cells were shown to be essential to the mechanism by which MYC or BCR-ABL inactivation elicits “oncogene withdrawal.” Hence, immune mediators contribute in multiple ways to the pathogenesis, prevention, and treatment of cancer, including mechanisms of tumor initiation, progression, and surveillance, but also oncogene inactivation-mediated tumor regression. Data from both the bench and the bedside illustrates that the inactivation of a driver oncogene can induce activation of the immune system that appears to be essential for sustained tumor regression.
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Affiliation(s)
- Stephanie C Casey
- Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, 269 Campus Drive, CCSR 1105, Stanford 94305-5151, CA, USA
| | - Yulin Li
- Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, 269 Campus Drive, CCSR 1105, Stanford 94305-5151, CA, USA
| | - Alice C Fan
- Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, 269 Campus Drive, CCSR 1105, Stanford 94305-5151, CA, USA
| | - Dean W Felsher
- Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, 269 Campus Drive, CCSR 1105, Stanford 94305-5151, CA, USA
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21
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Smieliauskas F, Chien CR, Shen C, Geynisman DM, Shih YCT. Cost-effectiveness analyses of targeted oral anti-cancer drugs: a systematic review. PHARMACOECONOMICS 2014; 32:651-680. [PMID: 24821281 DOI: 10.1007/s40273-014-0160-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/03/2023]
Abstract
BACKGROUND Over the last 15 years, a paradigm shift in oncology has led to the approval of dozens of targeted oral anti-cancer medications (OAMs), which have become the standard of care for certain cancers. While more convenient for patients than infused drugs, the possibility of non-adherence and the frequently high costs of targeted OAMs have proven controversial. OBJECTIVE Our objective was to perform the first comprehensive review of cost-effectiveness analyses (CEAs) of targeted OAMs. METHODS A literature search in PubMed, The Cochrane Library, and the Health Technology Assessment (HTA) reports published by the National Institute for Health Research HTA Programme in the UK was performed, covering articles published in the 5 years prior to 30 September 2013. Our inclusion criteria were peer-reviewed English-language full-text original research articles with a primary focus on CEA related to targeted OAMs. We categorized these articles by treatment setting (i.e. cancer site/type, line of therapy, and treatment and comparator) and synthesized information from the articles into summary tables. RESULTS We identified 41 CEAs covering nine of the 18 targeted OAMs approved by the US FDA as of December 2012. These medications were studied in seven cancers, most often as second-line therapy for advanced-stage patients. In over half of treatment settings where a targeted OAM was compared with treatment that was not a targeted OAM, targeted OAMs were considered cost effective. Limitations in interpreting these findings include the risk of bias due to author conflicts of interest, cross-country variation, and difficulties in generalizing clinical trial evidence to community practice. CONCLUSIONS Several types of cost-effectiveness studies remain under-represented in the literature on targeted OAMs, including those for follow-on indications approved after the initial indication for a drug and for off-label indications, head-to-head comparisons of targeted OAMs with other targeted OAMs and targeted intravenous therapies, and studies that adopt a perspective other than the payer's. Keeping up with the increasing number of approved targeted OAMs will also prove an important challenge for economic evaluation.
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Karikios DJ, Schofield D, Salkeld G, Mann KP, Trotman J, Stockler MR. Rising cost of anticancer drugs in Australia. Intern Med J 2014; 44:458-63. [DOI: 10.1111/imj.12399] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2013] [Accepted: 02/19/2014] [Indexed: 11/26/2022]
Affiliation(s)
- D. J. Karikios
- NHMRC Clinical Trials Centre; University of Sydney; Sydney New South Wales Australia
| | - D. Schofield
- NHMRC Clinical Trials Centre; University of Sydney; Sydney New South Wales Australia
| | - G. Salkeld
- Sydney School of Public Health; Sydney Medical School; University of Sydney; Sydney New South Wales Australia
| | - K. P. Mann
- NHMRC Clinical Trials Centre; University of Sydney; Sydney New South Wales Australia
| | - J. Trotman
- Concord Repatriation General Hospital; University of Sydney; Sydney New South Wales Australia
| | - M. R. Stockler
- NHMRC Clinical Trials Centre; University of Sydney; Sydney New South Wales Australia
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23
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Peixoto V, Faria AL, Gonçalves M, Macedo J, Rego S, Macías E, Magano A, Loureiro M, Araújo A. Evolution of costs of cancer drugs in a Portuguese hospital. World J Clin Oncol 2014; 5:164-169. [PMID: 24829864 PMCID: PMC4014789 DOI: 10.5306/wjco.v5.i2.164] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2013] [Revised: 02/18/2014] [Accepted: 03/04/2014] [Indexed: 02/06/2023] Open
Abstract
AIM: To analyze the costs of cancer drugs administered in a Portuguese Hospital compared with the Karolinska Institute study.
METHODS: To evaluate spending on cancer drugs, we retrospectively analyzed data on the overall costs of cancer drugs, obtained at the Department of Medical Oncology of the Centro Hospitalar de Entre Douro e Vouga, between 2004 and 2010. In this comparative study we selected only drugs belonging to the following groups: chemotherapy, targeted therapy, immunotherapy and endocrine therapy. The selected drugs were further grouped according to their market placement year: ≤ 1998, 1999 to 2002, 2003 to 2005, and 2006 to 2010. Drugs used as supportive therapy and bisphosphonates were excluded.
RESULTS: The overall costs of cancer drugs increased gradually between 2004 and 2008 (from €1911947 to €3666284), with an increase in the number of patients treated during this period. The expenditure decreased in 2009 (€3438155) and increased again in 2010 (€3673116), but the costs increment was not the same as in previous years. Chemotherapy and targeted therapy were responsible for most of the expenditure. Drugs placed on the national market before 1999 accounted for more than 50% of the expenditure up to 2007. From 2008, these drugs represented less than 50% of the total expenditure. Cancer drugs placed between 1999 and 2002 accounted for 25%-35% of the costs in all the years studied, while drugs placed between 2003 and 2005 accounted for less than 30%. Drugs placed between 2006 and 2010 were responsible for less than 10% of the expenditure.
CONCLUSION: In this study, older drugs were responsible for most of the expenditure up to 2007, which is in agreement with the Karolinska study.
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Casey SC, Li Y, Felsher DW. An essential role for the immune system in the mechanism of tumor regression following targeted oncogene inactivation. Immunol Res 2014; 58:282-91. [PMID: 24791942 PMCID: PMC4201505 DOI: 10.1007/s12026-014-8503-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Tumors are genetically complex and can have a multitude of mutations. Consequently, it is surprising that the suppression of a single oncogene can result in rapid and sustained tumor regression, illustrating the concept that cancers are often "oncogene addicted." The mechanism of oncogene addiction has been presumed to be largely cell autonomous as a consequence of the restoration of normal physiological programs that induce proliferative arrest, apoptosis, differentiation, and/or cellular senescence. Interestingly, it has recently become apparent that upon oncogene inactivation, the immune response is critical in mediating the phenotypic consequences of oncogene addiction. In particular, CD4(+) T cells have been suggested to be essential to the remodeling of the tumor microenvironment, including the shutdown of host angiogenesis and the induction of cellular senescence in the tumor. However, adaptive and innate immune cells are likely involved. Thus, the effectors of the immune system are involved not only in tumor initiation, tumor progression, and immunosurveillance, but also in the mechanism of tumor regression upon targeted oncogene inactivation. Hence, oncogene inactivation may be an effective therapeutic approach because it both reverses the neoplastic state within a cancer cell and reactivates the host immune response that remodels the tumor microenvironment.
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Affiliation(s)
- Stephanie C Casey
- Division of Oncology, Departments of Medicine and Pathology, Stanford University School of Medicine, 269 Campus Drive, CCSR 1105, Stanford, CA, 94305-5151, USA
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25
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Lawler M, Le Chevalier T, Murphy MJ, Banks I, Conte P, De Lorenzo F, Meunier F, Pinedo H, Selby P, Armand JP, Barbacid M, Barzach M, Bergh J, Bode G, Cameron DA, de Braud F, de Gramont A, Diehl V, Diler S, Erdem S, Fitzpatrick JM, Geissler J, Hollywood D, Højgaard L, Horgan D, Jassem J, Johnson PW, Kapitein P, Kelly J, Kloezen S, La Vecchia C, Löwenberg B, Oliver K, Sullivan R, Tabernero J, Van de Velde CJ, Wilking N, Wilson R, Zielinski C, zur Hausen H, Johnston PG. A catalyst for change: the European cancer Patient's Bill of Rights. Oncologist 2014; 19:217-24. [PMID: 24493667 PMCID: PMC3958470 DOI: 10.1634/theoncologist.2013-0452] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2013] [Accepted: 01/06/2014] [Indexed: 11/17/2022] Open
Abstract
The European Cancer Concord is a unique patient-centered partnership that will act as a catalyst to achieve improved access to an optimal standard of cancer care and research for European citizens. In order to provide tangible benefits for European cancer patients, the partnership proposes the creation of a “European Cancer Patient’s Bill of Rights,” a patient charter that will underpin equitable access to an optimal standard of care for Europe’s citizens.
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Affiliation(s)
- Mark Lawler
- Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, Belfast, United Kingdom
| | | | - Martin J. Murphy
- European Cancer Concord, Society for Translational Oncology, Durham, North Carolina, USA
| | - Ian Banks
- European Men’s Health Forum, Brussels, Belgium
| | | | - Francesco De Lorenzo
- Italian Federation of Volunteer-based Cancer Organizations, Rome, Italy
- European Cancer Patient Coalition, Brussels, Belgium
| | - Françoise Meunier
- European Organisation for Research and Treatment of Cancer, Brussels, Belgium
| | - H.M. Pinedo
- VuMC Cancer Center, Amsterdam, The Netherlands
| | - Peter Selby
- Department of Medical Oncology, University of Leeds, Leeds, United Kingdom
| | | | | | | | - Jonas Bergh
- Department of Oncology-Pathology, Karolinska Institut, Stockholm, Sweden
| | - Gerlind Bode
- International Confederation of Childhood Cancer Parent Organizations, Nieuwegein, The Netherlands
| | - David A. Cameron
- Edinburgh Cancer Centre, NHS Lothian & Edinburgh Cancer Research Centre, University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom
| | - Filippo de Braud
- Medical Oncology Division, National Cancer Institute, Milan, Italy
| | | | - Volker Diehl
- Internal Medicine, University of Cologne, Köln, Germany
| | | | - Sema Erdem
- Europa Donna, Piazza Amendola, Milan, Italy
| | - John M. Fitzpatrick
- Irish Cancer Society, Dublin, Ireland
- Department of Surgery, University College Dublin, Dublin, Ireland
| | - Jan Geissler
- Leukemia Patient Advocates Foundation, Berne, Switzerland
- European Patients Academy on Therapeutic Innovation, Riemerling, Germany
| | - Donal Hollywood
- >† Deceased
- Academic Unit of Clinical and Molecular Oncology, St James’s Hospital and Trinity College Dublin, Dublin, Ireland
| | - Liselotte Højgaard
- Danish National Research Foundation, Copenhagen, Denmark
- Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
| | - Denis Horgan
- European Alliance for Personalised Medicine, Brussels, Belgium
| | - Jacek Jassem
- Department of Oncology and Radiotherapy, Medical University of Gdansk, Gdansk, Poland
| | - Peter W. Johnson
- Department of Medical Oncology, University of Southampton, Southampton, United Kingdom
- Cancer Research UK, London, United Kingdom
| | | | - Joan Kelly
- Irish Cancer Society, Dublin, Ireland
- European Cancer Leagues, Brussels, Belgium
| | | | - Carlo La Vecchia
- Dipartimento di Epidemiologia, Istituto di Ricerche Farmacologiche “Mario Negri” Milan, Italy
| | - Bob Löwenberg
- Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - Kathy Oliver
- International Brain Tumor Alliance, Tadworth, Surrey, United Kingdom
| | - Richard Sullivan
- Institute of Cancer Policy, Kings Health Partners Integrated Cancer Centre, London, United Kingdom
| | | | | | - Nils Wilking
- Department of Oncology, Karolinska Institut, Stockholm, Sweden, and Skåne University Hospital, Lund, Sweden
| | | | - Christoph Zielinski
- Comprehensive Cancer Center and Department of Medicine I, Medical University Vienna - General Hospital, Vienna, Austria
| | - Harald zur Hausen
- German Cancer Research Centre, University of Heidelberg, Heidelberg, Germany
| | - Patrick G. Johnston
- Centre for Cancer Research and Cell Biology, School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, Belfast, United Kingdom
- School of Medicine, Dentistry and Biomedical Sciences, and Institute of Health Sciences, Queens University Belfast, Belfast, United Kingdom
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Modulation of c-kit expression in pancreatic adenocarcinoma: a novel stem cell marker responsible for the progression of the disease. Acta Histochem 2014; 116:197-203. [PMID: 23978330 DOI: 10.1016/j.acthis.2013.07.002] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2013] [Revised: 07/01/2013] [Accepted: 07/02/2013] [Indexed: 12/17/2022]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers because of late symptoms and resistance to chemotherapy and radiation therapy. We have investigated the appearance of c-kit, a stem cell marker, in both normal adult pancreatic tissue and in cancerous tissue. Apart from some very pale staining of islets of Langerhans, normal pancreas was devoid of staining with antibodies to c-kit. In contrast, in cancerous tissue that still preserves the overall integrity of the pancreatic tissue, there was a clear labeling in islets of Langerhans, which seemed to be co-localized with insulin containing β cells. In other cases, where the pancreatic tissue was completely deteriorated, intensive labeling was clearly evident in remnants of both the exocrine and the endocrine tissues. The duct cells of the adenocarcinoma were moderately but clearly labeled with antibodies to c-kit. In contrast, in metastasis of PDAC, very intensive labeling of c-kit was evident. The location of KRAS, which is strongly associated with PDAC, was also analyzed at the initial stages of the disease, when islets of Langerhans still preserve their integrity to a large extent. KRAS was found exclusively in islets of Langerhans and overlapped in its location with insulin and c-kit expressing cells. It is suggested that the modulation of the expression of c-kit, visualized by antibodies to the oncogene molecule, may play an important role in the formation and progression of PDAC. The absence of c-kit in normal pancreas and its appearance in PDAC is probably due to a mutational event, which probably allows conversion of the β cells into cancer stem cells (CSC). Co-expression of both c-kit and KRAS, typical markers for CSC with overlapping with insulin in islets of Langerhans, strongly support the notion that β-cells play a central role in the development of PDAC. The use of specific drugs that can attenuate the kinase activity of c-kit or target KRAS expressing cancer cells should be tested in order to attenuate the progression of this lethal disease.
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27
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Shen C, Chien CR, Geynisman DM, Smieliauskas F, Shih YCT. A review of economic impact of targeted oral anticancer medications. Expert Rev Pharmacoecon Outcomes Res 2013; 14:45-69. [PMID: 24378038 DOI: 10.1586/14737167.2014.868310] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
There has been a rapid increase in the use of targeted oral anticancer medications (OAMs) in the past decade. As OAMs are often expensive, economic consideration play a significant role in the decision to prescribe, receive or cover them. This paper performs a systematic review of costs or budgetary impact of targeted OAMs to better understand their economic impact on the healthcare system, patients as well as payers. We present our review in a summary table that describes the method and main findings, take into account multiple factors, such as country, analytical approach, cost type, study perspective, timeframe, data sources, study population and care setting when we interpret the results from different papers, and discuss the policy and clinical implications. Our review raises a concern regarding the role of sponsorship on findings of economic analyses as the vast majority of pharmaceutical company-sponsored studies reported cost advantages toward the sponsor's drugs.
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Affiliation(s)
- Chan Shen
- Departments of Health Services Research and Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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28
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Noh GT, Kim MH, Suh JY, Song Y, Lee CK, Baek JH, Lee YS, Cho G, Kim E, Kim YR, Cho HJ, Lim D, Kim JK. Sunitinib--CLIO conjugate: a VEGFR/PDGFR-targeting active MR probe. Mol Imaging Biol 2013; 16:340-9. [PMID: 24185817 DOI: 10.1007/s11307-013-0697-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2013] [Revised: 09/10/2013] [Accepted: 10/02/2013] [Indexed: 12/11/2022]
Abstract
PURPOSE This study was conducted to evaluate feasibility of sunitinib-CLIO conjugate as a vascular endothelial growth factor receptor/platelet-derived growth factor receptor (VEGFR/PDGFR)-specific magnetic resonance (MR) probe. PROCEDURE VEGFR/PDGFR-targeting MR probe was synthesized by conjugating cross-linked iron-oxide (CLIO) with tyrosine-kinase inhibitor (sunitinib). In VEGFR/PDGFR-positive (U118MG) and VEGFR/PDGFR-negative (HT29) cells and tumor models, conjugate-driven ΔR 2 was estimated, while CLIO was used as control. Prussian-blue staining was performed for quantifying the amount of tumor-binding conjugates. RESULTS ΔR 2 between sunitinib-CLIO-treated and non-treated cells was greater in U118MG (mean, 2.1/s) than in HT29 cells (1.0/s). In in vivo study, conjugate induced a greater ΔR 2 in U118MG (11.2/s) than HT29 tumors (5.9/s). Conjugate-induced R 2 changes were not correlated with degree of Gd-DTPA enhancement, demonstrating that tumor binding of sunitinib-CLIO was independent of enhanced permeability and retention effect. % area of Prussian-blue staining was greater in U118MG (8.5 %) than in HT29 (1.4 %). CONCLUSIONS Sunitinib-CLIO conjugate can be used as an active MR probe for quantifying VEGFR/PDGFR.
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Affiliation(s)
- Gwang Tae Noh
- Department of Chemistry, Sejong University, Seoul, 143-747, South Korea
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Noncanonical roles of the immune system in eliciting oncogene addiction. Curr Opin Immunol 2013; 25:246-58. [PMID: 23571026 DOI: 10.1016/j.coi.2013.02.003] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2012] [Revised: 02/07/2013] [Accepted: 02/08/2013] [Indexed: 02/08/2023]
Abstract
Cancer is highly complex. The magnitude of this complexity makes it highly surprising that even the brief suppression of an oncogene can sometimes result in rapid and sustained tumor regression, illustrating that cancers can be 'oncogene addicted' [1-10]. The essential implication is that oncogenes may not only fuel the initiation of tumorigenesis, but in some cases must be excessively activated to maintain a neoplastic state [11]. Oncogene suppression acutely restores normal physiological programs that effectively overrides secondary genetic events and a cancer collapses [12,13]. Oncogene addiction is the description of the dramatic and sustained regression of some cancers upon the specific inactivation of a single oncogene [1-13,14(••),15,16(••)], that can occur through tumor intrinsic [1,2,4,12], but also host immune mechanisms [17-23]. Notably, oncogene inactivation elicits a host immune response that involves specific immune effectors and cytokines that facilitate a remodeling of the tumor microenvironment including the shut down of angiogenesis and the induction of cellular senescence of tumor cells [16(••)]. Hence, immune effectors are not only critically involved in tumor prevention, initiation [17-19], and progression [20], but also appear to be essential to tumor regression upon oncogene inactivation [21,22(••),23(••)]. Understanding how the inactivation of an oncogene elicits a systemic signal in the host that prompts a deconstruction of a tumor could have important implications. The combination of oncogene-targeted therapy together with immunomodulatory therapy may be ideal for the development of both robust tumor intrinsic and immunological responses, effectively leading to sustained tumor regression.
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Davis SJ, Sheppard KE, Pearson RB, Campbell IG, Gorringe KL, Simpson KJ. Functional analysis of genes in regions commonly amplified in high-grade serous and endometrioid ovarian cancer. Clin Cancer Res 2013; 19:1411-21. [PMID: 23362323 DOI: 10.1158/1078-0432.ccr-12-3433] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
PURPOSE Ovarian cancer has the highest mortality rate of all the gynecologic malignancies and is responsible for approximately 140,000 deaths annually worldwide. Copy number amplification is frequently associated with the activation of oncogenic drivers in this tumor type, but their cytogenetic complexity and heterogeneity has made it difficult to determine which gene(s) within an amplicon represent(s) the genuine oncogenic driver. We sought to identify amplicon targets by conducting a comprehensive functional analysis of genes located in the regions of amplification in high-grade serous and endometrioid ovarian tumors. EXPERIMENTAL DESIGN High-throughput siRNA screening technology was used to systematically assess all genes within regions commonly amplified in high-grade serous and endometrioid cancer. We describe the results from a boutique siRNA screen of 272 genes in a panel of 18 ovarian cell lines. Hits identified by the functional viability screen were further interrogated in primary tumor cohorts to determine the clinical outcomes associated with amplification and gene overexpression. RESULTS We identified a number of genes as critical for cellular viability when amplified, including URI1, PAK4, GAB2, and DYRK1B. Integration of primary tumor gene expression and outcome data provided further evidence for the therapeutic use of such genes, particularly URI1 and GAB2, which were significantly associated with survival in 2 independent tumor cohorts. CONCLUSION By taking this integrative approach to target discovery, we have streamlined the translation of high-resolution genomic data into preclinical in vitro studies, resulting in the identification of a number of genes that may be specifically targeted for the treatment of advanced ovarian tumors.
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Affiliation(s)
- Sally J Davis
- Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia
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31
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Current world literature. Curr Opin Oncol 2012; 24:756-68. [PMID: 23079785 DOI: 10.1097/cco.0b013e32835a4c91] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
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Bachet JB, Maréchal R, Demetter P, Bonnetain F, Couvelard A, Svrcek M, Bardier-Dupas A, Hammel P, Sauvanet A, Louvet C, Paye F, Rougier P, Penna C, Vaillant JC, André T, Closset J, Salmon I, Emile JF, Van Laethem JL. Contribution of CXCR4 and SMAD4 in predicting disease progression pattern and benefit from adjuvant chemotherapy in resected pancreatic adenocarcinoma. Ann Oncol 2012; 23:2327-2335. [PMID: 22377565 DOI: 10.1093/annonc/mdr617] [Citation(s) in RCA: 58] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Prognosis of patients with pancreatic adenocarcinoma is poor. Many prognostic biomarkers have been tested, but most studies included heterogeneous patients. We aimed to investigate the prognostic and/or predictive values of four relevant biomarkers in a multicentric cohort of patients. PATIENTS AND METHODS A total of 471 patients who had resected pancreatic adenocarcinoma were included. Using tissue microarray, we assessed the relationship of biomarker expressions with the overall survival: Smad4, type II TGF-β receptor, CXCR4, and LKB1. RESULTS High CXCR4 expression was found to be the only independent negative prognostic biomarker [hazard ratio (HR) = 1.74; P < 0.0001]. In addition, it was significantly associated with a distant relapse pattern (HR = 2.19; P < 0.0001) and was the strongest prognostic factor compared with clinicopathological factors. In patients who did not received adjuvant treatment, there was a trend toward decrease in the overall survival for negative Smad4 expression. Loss of Smad4 expression was not correlated with recurrence pattern but was shown to be predictive for adjuvant chemotherapy (CT) benefit (HR = 0.59; P = 0.002). CONCLUSIONS CXCR4 is a strong independent prognostic biomarker associated with distant metastatic recurrence and appears as an attractive target to be evaluated in pancreatic adenocarcinoma. Negative SMAD4 expression should be considered as a potential predictor of adjuvant CT benefit.
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Affiliation(s)
- J B Bachet
- Medical University Pierre et Marie Curie, UFR Paris VI, Paris; EA4340 "Epidémiologie et oncogènes des tumeurs digestives", Versailles Saint-Quentin-en-Yvelines University, Versailles; Department of Hepato-Gastroenterology, Pitié-Salpêtrière Hospital, APHP, Paris, France; Department of Gastroenterology, Gastrointestinal cancer Unit, Erasme Hospital, Université Libre de Bruxelles, Brussels.
| | - R Maréchal
- Department of Gastroenterology, Gastrointestinal cancer Unit, Erasme Hospital, Université Libre de Bruxelles, Brussels
| | - P Demetter
- Department of Pathology, Erasme Hospital, Université Libre de Bruxelles, and DiaPath, Brussels, Belgium
| | - F Bonnetain
- Department of Biostatistic and Epidemiology (EA 4184), Georges François Leclerc Center, Dijon
| | - A Couvelard
- Department of Pathology, Beaujon Hospital, APHP, Clichy
| | - M Svrcek
- Medical University Pierre et Marie Curie, UFR Paris VI, Paris; Department of Pathology, Saint Antoine Hospital, APHP, Paris
| | - A Bardier-Dupas
- Medical University Pierre et Marie Curie, UFR Paris VI, Paris; Department of Pathology, Pitié-Salpêtrière Hospital, APHP, Paris
| | - P Hammel
- Department of Gastroenterology, Beaujon Hospital, APHP, Clichy
| | - A Sauvanet
- Department of Surgery, Beaujon Hospital, APHP, Clichy
| | - C Louvet
- Medical University Pierre et Marie Curie, UFR Paris VI, Paris; Department of Oncology, Saint Antoine Hospital, APHP, Paris; Department of Oncology, Institut Mutualiste Montsouris, Paris
| | - F Paye
- Medical University Pierre et Marie Curie, UFR Paris VI, Paris; Department of Surgery, Saint Antoine Hospital, APHP, Paris
| | - P Rougier
- EA4340 "Epidémiologie et oncogènes des tumeurs digestives", Versailles Saint-Quentin-en-Yvelines University, Versailles; Department of Digestive Oncology, European Georges Pompidou Hospital, APHP, Paris
| | - C Penna
- EA4340 "Epidémiologie et oncogènes des tumeurs digestives", Versailles Saint-Quentin-en-Yvelines University, Versailles; Department of Surgery, Ambroise Paré Hospital, APHP, Boulogne-Billancourt
| | - J C Vaillant
- Medical University Pierre et Marie Curie, UFR Paris VI, Paris; Department of Surgery, Pitié-Salpêtrière Hospital, APHP, Paris, France
| | - T André
- Medical University Pierre et Marie Curie, UFR Paris VI, Paris; Department of Hepato-Gastroenterology, Pitié-Salpêtrière Hospital, APHP, Paris, France
| | - J Closset
- Department of Surgery, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
| | - I Salmon
- Department of Pathology, Erasme Hospital, Université Libre de Bruxelles, and DiaPath, Brussels, Belgium
| | - J F Emile
- EA4340 "Epidémiologie et oncogènes des tumeurs digestives", Versailles Saint-Quentin-en-Yvelines University, Versailles; Department of Pathology, Ambroise Paré Hospital, APHP, Boulogne-Billancourt, France
| | - J L Van Laethem
- Department of Gastroenterology, Gastrointestinal cancer Unit, Erasme Hospital, Université Libre de Bruxelles, Brussels
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Economic Evaluation of Anastrozole Versus Tamoxifen for Early Stage Breast Cancer in Singapore. Value Health Reg Issues 2012; 1:46-53. [DOI: 10.1016/j.vhri.2012.03.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
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Valachis A, Polyzos NP, Nearchou A, Lind P, Mauri D. Financial relationships in economic analyses of targeted therapies in oncology. J Clin Oncol 2012; 30:1316-20. [PMID: 22430267 DOI: 10.1200/jco.2011.38.6078] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
PURPOSE A potential financial relationship between investigators and pharmaceutical manufacturers has been associated with an increased likelihood of reporting favorable conclusions about a sponsor's proprietary agent in pharmacoeconomic studies. The purpose of this study is to investigate whether there is an association between financial relationships and outcome in economic analyses of new targeted therapies in oncology. MATERIALS AND METHODS We searched PubMed (last update June 2011) for economic analyses of targeted therapies (including monoclonal antibodies, tyrosine-kinase inhibitors, and mammalian target of rapamycin inhibitors) in oncology. The trials were qualitatively rated regarding the cost assessment as favorable, neutral, or unfavorable on the basis of prespecified criteria. RESULTS Overall, 81 eligible studies were identified. Economic analyses that were funded by pharmaceutical companies were more likely to report favorable qualitative cost estimates (28 [82%] of 34 v 21 [45%] of 47; P = .003). The presence of an author affiliated with manufacturer was not associated with study outcome. Furthermore, if only studies including a conflict of interest statement were included (66 of 81), studies that reported any financial relationship with manufacturers (author affiliation and/or funding and/or other financial relationship) were more likely to report favorable results of targeted therapies compared with studies without financial relationship (32 [71%] of 45 v nine [43%] of 21; P = .025). CONCLUSION Our study reveals a potential threat for industry-related bias in economic analyses of targeted therapies in oncology in favor of analyses with financial relationships between authors and manufacturers. A more balanced funding of economic analyses from other sources may allow greater confidence in the interpretation of their results.
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Pivot X, Jary M, Dobi E, Bazan F, Chaigneau L, Cals L, Almotlak H, Montcuquet P, Meneveau N, Villanueva C. Cancer du sein métastatique surexprimant HER2 : évolutions des thérapeutiques. ONCOLOGIE 2012. [DOI: 10.1007/s10269-011-2106-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Are the large pharmaceutical and biotechnology companies driving the discovery, research and development of targeted cancer therapies? Future Med Chem 2012; 4:13-7. [DOI: 10.4155/fmc.11.164] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
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Keefe DMK, Bateman EH. Tumor control versus adverse events with targeted anticancer therapies. Nat Rev Clin Oncol 2011; 9:98-109. [DOI: 10.1038/nrclinonc.2011.192] [Citation(s) in RCA: 77] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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Abstract
Carcinomas of an unknown primary origin (CUP) account for 3-5% of all malignancies and are thus among the ten most-frequent cancers worldwide. Having a specific and unique phenotype of early and usually aggressive metastatic dissemination with no identifiable primary tumor, CUP are a challenge for physicians. The diagnostic workup of patients with CUP includes a careful clinical and extensive histopathological examination, as well as the use of imaging techniques. CUP can be divided into favorable and unfavorable subsets. Patients with unfavorable CUP subsets have a poor prognosis with a median survival of approximately 8 months; the optimal chemotherapy regimen for these patients remains to be determined. Although studies have focused on the introduction of new cytotoxic agents with broad-spectrum clinical activity (such as gemcitabine, irinotecan, and taxanes), no randomized trial has provided clear evidence of a survival benefit. Molecular targeted therapies that are approved for other solid tumors are now considered for the treatment of patients with CUP. Molecular diagnostic tools, such as DNA microarray analysis, could help in the search for 'lost' CUP origins. In this Review, we describe the clinical evaluation of patients with CUP, and discuss treatment strategies and outcomes of patients with various CUP subsets.
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Mordant P, Loriot Y, Lahon B, Castier Y, Lesèche G, Soria JC, Vozenin MC, Decraene C, Deutsch E. Bioluminescent orthotopic mouse models of human localized non-small cell lung cancer: feasibility and identification of circulating tumour cells. PLoS One 2011; 6:e26073. [PMID: 22022511 PMCID: PMC3191172 DOI: 10.1371/journal.pone.0026073] [Citation(s) in RCA: 41] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2011] [Accepted: 09/19/2011] [Indexed: 01/09/2023] Open
Abstract
Background Preclinical models of non-small cell lung cancer (NSCLC) require better clinical relevance to study disease mechanisms and innovative therapeutics. We sought to compare and refine bioluminescent orthotopic mouse models of human localized NSCLC. Methods Athymic nude mice underwent subcutaneous injection (group 1-SC, n = 15, control), percutaneous orthotopic injection (group 2-POI, n = 30), surgical orthotopic implantation of subcutaneously grown tumours (group 3-SOI, n = 25), or transpleural orthotopic injection (group 4-TOI, n = 30) of A549-luciferase cells. Bioluminescent in vivo imaging was then performed weekly. Circulating tumour cells (CTCs) were searched using Cellsearch® system in SC and TOI models. Results Group 2-POI was associated with unexpected direct pleural spreading of the cellular solution in 53% of the cases, forbidding further evaluation of any localized lung tumour. Group 3-SOI was characterized by high perioperative mortality, initially localized lung tumours, and local evolution. Group 4-TOI was associated with low perioperative mortality, initially localized lung tumours, loco regional extension, and distant metastasis. CTCs were detected in 83% of nude mice bearing subcutaneous or orthotopic NSCLC tumours. Conclusions Transpleural orthotopic injection of A549-luc cells in nude mouse lung induces localized tumour, followed by lymphatic extension and specific mortality, and allowed the first time identification of CTCs in a NSCLC mice model.
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Affiliation(s)
- Pierre Mordant
- INSERM U1030 & Université Paris XI, Institut Gustave Roussy, Villejuif, France
- Service de Chirurgie Thoracique & Université Paris VII, Hôpital Bichat, AP-HP, Paris, France
| | - Yohann Loriot
- INSERM U1030 & Université Paris XI, Institut Gustave Roussy, Villejuif, France
- Département de Médecine, SITEP& Université Paris XI, Institut Gustave Roussy, Villejuif, France
| | - Benoit Lahon
- INSERM U1030 & Université Paris XI, Institut Gustave Roussy, Villejuif, France
| | - Yves Castier
- Service de Chirurgie Thoracique & Université Paris VII, Hôpital Bichat, AP-HP, Paris, France
| | - Guy Lesèche
- Service de Chirurgie Thoracique & Université Paris VII, Hôpital Bichat, AP-HP, Paris, France
| | - Jean-Charles Soria
- Département de Médecine, SITEP& Université Paris XI, Institut Gustave Roussy, Villejuif, France
| | | | - Charles Decraene
- Département de Recherche translationnelle, Institut Curie, Paris, France
- CNRS UMR144, Paris, France
| | - Eric Deutsch
- INSERM U1030 & Université Paris XI, Institut Gustave Roussy, Villejuif, France
- Département de Radiothérapie & Université Paris XI, Institut Gustave Roussy, Villejuif, France
- * E-mail:
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McLeod H, Tortora G, Rowett L, Vermorken J. Found in translation: Annals of Oncology and translational research. Ann Oncol 2011; 22:1698-1699. [DOI: 10.1093/annonc/mdr342] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/30/2023] Open
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