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Chen M, Liu H, Xiao Y, Liang R, Xu H, Hong B, Qian Y. Predictive biomarkers of pancreatic cancer metastasis: A comprehensive review. Clin Chim Acta 2025; 569:120176. [PMID: 39914505 DOI: 10.1016/j.cca.2025.120176] [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: 01/12/2025] [Revised: 01/26/2025] [Accepted: 01/28/2025] [Indexed: 02/12/2025]
Abstract
This review provides a comprehensive overview of predictive biomarkers associated with metastasis in pancreatic cancer (PC), one of the most aggressive malignancies characterized by late-stage diagnosis and poor prognosis. Metastasis, particularly to the liver, lungs, and lymph nodes, significantly worsens patient outcomes by compromising organ function and promoting disease progression. Reliable biomarkers for predicting and detecting metastasis at early stages are critical for improving survival rates and guiding personalized therapies. This paper highlights both general and specific biomarkers, including genetic mutations, protein expression changes, and carbohydrate tumor markers such as CA19-9. Immunological factors, including PD-L1, inflammatory cytokines, and chemokines, further influence the metastatic process within the tumor microenvironment (TME). Specific biomarkers play pivotal roles in promoting metastasis through mechanisms such as epithelial-to-mesenchymal transition (EMT), tumor microenvironment remodeling, and immune evasion. Emerging markers such as circulating tumor cells (CTCs) and volatile organic compounds (VOCs) offer promising non-invasive tools for metastasis detection and monitoring. This review not only consolidates existing knowledge but also highlights the mechanisms through which specific biomarkers facilitate metastasis. Despite recent progress, challenges such as biomarker standardization, technical variability, and clinical validation remain, and addressing these hurdles is essential for integrating predictive biomarkers into clinical practice. Ultimately, this review contributes to advancing early detection strategies, personalized treatment options, and improved prognosis for PC patients.
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Affiliation(s)
- Mengting Chen
- Department of Clinical Laboratory, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou 310000, China
| | - Hongsen Liu
- Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou 310000, China
| | - Yufei Xiao
- Department of Clinical Laboratory, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China
| | - Ruijin Liang
- The Queen's University of Belfast Joint College, China Medical University, Shenyang 110122, China
| | - Hong Xu
- Departments of Pathology, Quzhou Second People's Hospital, Quzhou 324022, China
| | - Bo Hong
- Department of Pathology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
| | - Yun Qian
- Department of Clinical Laboratory, Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Hangzhou 310000, China.
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Du Y, Yang Y, Zheng B, Zhang Q, Zhou S, Zhao L. Finding a needle in a haystack: functional screening for novel targets in cancer immunology and immunotherapies. Oncogene 2025; 44:409-426. [PMID: 39863748 PMCID: PMC11810799 DOI: 10.1038/s41388-025-03273-8] [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: 09/18/2024] [Revised: 12/06/2024] [Accepted: 01/14/2025] [Indexed: 01/27/2025]
Abstract
Genome-wide functional genetic screening has been widely used in the biomedicine field, which makes it possible to find a needle in a haystack at the genetic level. In cancer research, gene mutations are closely related to tumor development, metastasis, and recurrence, and the use of state-of-the-art powerful screening technologies, such as clustered regularly interspaced short palindromic repeat (CRISPR), to search for the most critical genes or coding products provides us with a new possibility to further refine the cancer mapping and provide new possibilities for the treatment of cancer patients. The use of CRISPR screening for the most critical genes or coding products has further refined the cancer atlas and provided new possibilities for the treatment of cancer patients. Immunotherapy, as a highly promising cancer treatment method, has been widely validated in the clinic, but it could only meet the needs of a small proportion of cancer patients. Finding new immunotherapy targets is the key to the future of tumor immunotherapy. Here, we revisit the application of functional screening in cancer immunology from different perspectives, from the selection of diverse in vitro and in vivo screening models to the screening of potential immune checkpoints and potentiating genes for CAR-T cells. The data will offer fresh therapeutic clues for cancer patients.
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Affiliation(s)
- Yi Du
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second Hospital, State Key Laboratory of Biotherapy, and Department of Neurosurgery, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P. R. China
| | - Yang Yang
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second Hospital, State Key Laboratory of Biotherapy, and Department of Neurosurgery, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P. R. China
| | - Bohao Zheng
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second Hospital, State Key Laboratory of Biotherapy, and Department of Neurosurgery, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P. R. China
- Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China
| | - Qian Zhang
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second Hospital, State Key Laboratory of Biotherapy, and Department of Neurosurgery, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P. R. China.
| | - Shengtao Zhou
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second Hospital, State Key Laboratory of Biotherapy, and Department of Neurosurgery, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P. R. China.
| | - Linjie Zhao
- Department of Obstetrics and Gynecology, Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second Hospital, State Key Laboratory of Biotherapy, and Department of Neurosurgery, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, P. R. China.
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Jiang M, Fang H, Tian H. Metabolism of cancer cells and immune cells in the initiation, progression, and metastasis of cancer. Theranostics 2025; 15:155-188. [PMID: 39744225 PMCID: PMC11667227 DOI: 10.7150/thno.103376] [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: 09/07/2024] [Accepted: 11/13/2024] [Indexed: 01/11/2025] Open
Abstract
The metabolism of cancer and immune cells plays a crucial role in the initiation, progression, and metastasis of cancer. Cancer cells often undergo metabolic reprogramming to sustain their rapid growth and proliferation, along with meeting their energy demands and biosynthetic needs. Nevertheless, immune cells execute their immune response functions through the specific metabolic pathways, either to recognize, attack, and eliminate cancer cells or to promote the growth or metastasis of cancer cells. The alteration of cancer niches will impact the metabolism of both cancer and immune cells, modulating the survival and proliferation of cancer cells, and the activation and efficacy of immune cells. This review systematically describes the key characteristics of cancer cell metabolism and elucidates how such metabolic traits influence the metabolic behavior of immune cells. Moreover, this article also highlights the crucial role of immune cell metabolism in anti-tumor immune responses, particularly in priming T cell activation and function. By comprehensively exploring the metabolic crosstalk between cancer and immune cells in cancer niche, the aim is to discover novel strategies of cancer immunotherapy and provide effective guidance for clinical research in cancer treatment. In addition, the review also discusses current challenges such as the inadequacy of relevant diagnostic technologies and the issue of multidrug resistance, and proposes potential solutions including bolstering foundational cancer research, fostering technological innovation, and implementing precision medicine approaches. In-depth research into the metabolic effects of cancer niches can improve cancer treatment outcomes, prolong patients' survival period and enhance their quality of life.
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Affiliation(s)
- Mingxia Jiang
- State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Xiamen University, Xiamen 361005, China
| | - Huapan Fang
- State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Xiamen University, Xiamen 361005, China
- Shenzhen Research Institute of Xiamen University, Shenzhen 518000, China
| | - Huayu Tian
- State Key Laboratory of Physical Chemistry of Solid Surfaces, College of Chemistry and Chemical Engineering, Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province (IKKEM), Xiamen University, Xiamen 361005, China
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Zhang Y, Qi F, Chen P, Liu BF, Li Y. Spatially defined microenvironment for engineering organoids. BIOPHYSICS REVIEWS 2024; 5:041302. [PMID: 39679203 PMCID: PMC11646138 DOI: 10.1063/5.0198848] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/19/2024] [Accepted: 10/01/2024] [Indexed: 12/17/2024]
Abstract
In the intricately defined spatial microenvironment, a single fertilized egg remarkably develops into a conserved and well-organized multicellular organism. This observation leads us to hypothesize that stem cells or other seed cell types have the potential to construct fully structured and functional tissues or organs, provided the spatial cues are appropriately configured. Current organoid technology, however, largely depends on spontaneous growth and self-organization, lacking systematic guided intervention. As a result, the structures replicated in vitro often emerge in a disordered and sparse manner during growth phases. Although existing organoids have made significant contributions in many aspects, such as advancing our understanding of development and pathogenesis, aiding personalized drug selection, as well as expediting drug development, their potential in creating large-scale implantable tissue or organ constructs, and constructing multicomponent microphysiological systems, together with functioning at metabolic levels remains underutilized. Recent discoveries have demonstrated that the spatial definition of growth factors not only induces directional growth and migration of organoids but also leads to the formation of assembloids with multiple regional identities. This opens new avenues for the innovative engineering of higher-order organoids. Concurrently, the spatial organization of other microenvironmental cues, such as physical stresses, mechanical loads, and material composition, has been minimally explored. This review delves into the burgeoning field of organoid engineering with a focus on potential spatial microenvironmental control. It offers insight into the molecular principles, expected outcomes, and potential applications, envisioning a future perspective in this domain.
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Affiliation(s)
- Yilan Zhang
- The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics and Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Fukang Qi
- The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics and Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Peng Chen
- The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics and Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Bi-Feng Liu
- The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics and Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Yiwei Li
- The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics-Hubei Bioinformatics and Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China
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Yang JL, Zhang JF, Gu JY, Gao M, Zheng MY, Guo SX, Zhang T. Strategic insights into the cultivation of pancreatic cancer organoids from endoscopic ultrasonography-guided biopsy tissue. World J Gastroenterol 2024; 30:4532-4543. [PMID: 39563744 PMCID: PMC11572629 DOI: 10.3748/wjg.v30.i42.4532] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2024] [Revised: 09/10/2024] [Accepted: 10/16/2024] [Indexed: 10/31/2024] Open
Abstract
BACKGROUND The frequent suboptimal efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) to culture pancreatic cancer (PC) organoids (PCOs) poses a major challenge in the advancement of personalized medicine for advanced PC. AIM To explore how to obtain appropriate puncture tissues from EUS-FNB and optimize the strategy for efficiently constructing PCOs, providing an efficient tool for the advancement of personalized medicine. METHODS Patients who underwent EUS-FNB for the diagnosis of PC tissue were prospectively enrolled. We refined the endoscopic biopsy procedures and organoid cultivation techniques. All tissue specimens verified by on-site pathological assessment were cultured in a semi-suspended medium in a microfluidic environment. We assessed differences in PCOs cultured beyond and below five generations examining patient demographics, specimen and organoid attributes, and the sensitivity of organoids to a panel of clinical drugs through cell viability assays. RESULTS In this study, 16 patients with PC were recruited, one sample was excluded because onsite cytopathology showed no tumor cells. Successful organoid generation occurred in 93.3% (14 of 15) of the EUS-FNB specimens, with 60% (9 of 15) sustaining over five generations. Among these patients, those with a history of diabetes, familial cancer, or larger tumors exhibited enhanced PCO expandability. The key factors influencing long-term PCOs expansion included initial needle sample quality (P = 0.005), rapid initiation of organoid culture post-isolation (P ≤ 0.001), and high organoid activity (P = 0.031). Drug sensitivity analysis revealed a partial response in two patients following therapeutic intervention and surgery and stable disease in four patients, indicating a moderate correlation between organoid response and clinical outcomes. CONCLUSION Optimal initial needle sampling, rapid and precise biopsy sample processing, process isolated samples as soon as possible, and sufficient cellular material are crucial for successful cultivating PCOs. High organoid activity is an important factor in maintaining their long-term expansion, which is essential for shortening the time of drug sensitivity analysis and is the basis of PC research.
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Affiliation(s)
- Jia-Li Yang
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China
| | - Jun-Feng Zhang
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China
| | - Jian-You Gu
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China
| | - Mei Gao
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China
| | - Ming-You Zheng
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China
| | - Shi-Xiang Guo
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China
| | - Tao Zhang
- Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, Chongqing University, Chongqing 401147, China
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Yang X, Wu H. RAS signaling in carcinogenesis, cancer therapy and resistance mechanisms. J Hematol Oncol 2024; 17:108. [PMID: 39522047 PMCID: PMC11550559 DOI: 10.1186/s13045-024-01631-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 11/01/2024] [Indexed: 11/16/2024] Open
Abstract
Variants in the RAS family (HRAS, NRAS and KRAS) are among the most common mutations found in cancer. About 19% patients with cancer harbor RAS mutations, which are typically associated with poor clinical outcomes. Over the past four decades, KRAS has long been considered an undruggable target due to the absence of suitable small-molecule binding sites within its mutant isoforms. However, recent advancements in drug design have made RAS-targeting therapies viable, particularly with the approval of direct KRASG12C inhibitors, such as sotorasib and adagrasib, for treating non-small cell lung cancer (NSCLC) with KRASG12C mutations. Other KRAS-mutant inhibitors targeting KRASG12D are currently being developed for use in the clinic, particularly for treating highly refractory malignancies like pancreatic cancer. Herein, we provide an overview of RAS signaling, further detailing the roles of the RAS signaling pathway in carcinogenesis. This includes a summary of RAS mutations in human cancers and an emphasis on therapeutic approaches, as well as de novo, acquired, and adaptive resistance in various malignancies.
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Affiliation(s)
- Xiaojuan Yang
- Liver Digital Transformation Research Laboratory, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P.R. China
| | - Hong Wu
- Liver Digital Transformation Research Laboratory, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P.R. China.
- Liver Transplantation Center, Liver Digital Transformation Research Laboratory, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center of Biotherapy, Chengdu, Sichuan, 610041, P.R. China.
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Zeng G, Yu Y, Wang M, Liu J, He G, Yu S, Yan H, Yang L, Li H, Peng X. Advancing cancer research through organoid technology. J Transl Med 2024; 22:1007. [PMID: 39516934 PMCID: PMC11545094 DOI: 10.1186/s12967-024-05824-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2024] [Accepted: 10/31/2024] [Indexed: 11/16/2024] Open
Abstract
The complexity of tumors and the challenges associated with treatment often stem from the limitations of existing models in accurately replicating authentic tumors. Recently, organoid technology has emerged as an innovative platform for tumor research. This bioengineering approach enables researchers to simulate, in vitro, the interactions between tumors and their microenvironment, thereby enhancing the intricate interplay between tumor cells and their surroundings. Organoids also integrate multidimensional data, providing a novel paradigm for understanding tumor development and progression while facilitating precision therapy. Furthermore, advancements in imaging and genetic editing techniques have significantly augmented the potential of organoids in tumor research. This review explores the application of organoid technology for more precise tumor simulations and its specific contributions to cancer research advancements. Additionally, we discuss the challenges and evolving trends in developing comprehensive tumor models utilizing organoid technology.
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Affiliation(s)
- Guolong Zeng
- Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China
| | - Yifan Yu
- Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China
| | - Meiting Wang
- Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China
| | - Jiaxing Liu
- Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China
| | - Guangpeng He
- Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China
| | - Sixuan Yu
- Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China
| | - Huining Yan
- Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China
| | - Liang Yang
- Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China.
- Shenyang Clinical Medical Research Center for Diagnosis, Treatment and Health Management of Early Digestive Cancer, Shenyang, China.
| | - Hangyu Li
- Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China.
- Shenyang Clinical Medical Research Center for Diagnosis, Treatment and Health Management of Early Digestive Cancer, Shenyang, China.
| | - Xueqiang Peng
- Department of General Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110032, China.
- Shenyang Clinical Medical Research Center for Diagnosis, Treatment and Health Management of Early Digestive Cancer, Shenyang, China.
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Zhao Y, Qin C, Lin C, Li Z, Zhao B, Li T, Zhang X, Wang W. Pancreatic ductal adenocarcinoma cells reshape the immune microenvironment: Molecular mechanisms and therapeutic targets. Biochim Biophys Acta Rev Cancer 2024; 1879:189183. [PMID: 39303859 DOI: 10.1016/j.bbcan.2024.189183] [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: 06/09/2024] [Revised: 08/23/2024] [Accepted: 09/13/2024] [Indexed: 09/22/2024]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a digestive system malignancy characterized by challenging early detection, limited treatment alternatives, and generally poor prognosis. Although there have been significant advancements in immunotherapy for hematological malignancies and various solid tumors in recent decades, with impressive outcomes in recent preclinical and clinical trials, the effectiveness of these therapies in treating PDAC continues to be modest. The unique immunological microenvironment of PDAC, especially the abnormal distribution, complex composition, and variable activation states of tumor-infiltrating immune cells, greatly restricts the effectiveness of immunotherapy. Undoubtedly, integrating data from both preclinical models and human studies helps accelerate the identification of reliable molecules and pathways responsive to targeted biological therapies and immunotherapies, thereby continuously optimizing therapeutic combinations. In this review, we delve deeply into how PDAC cells regulate the immune microenvironment through complex signaling networks, affecting the quantity and functional status of immune cells to promote immune escape and tumor progression. Furthermore, we explore the multi-modal immunotherapeutic strategies currently under development, emphasizing the transformation of the immunosuppressive environment into an anti-tumor milieu by targeting specific molecular and cellular pathways, providing insights for the development of novel treatment strategies.
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Affiliation(s)
- Yutong Zhao
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100023, PR China; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100023, PR China; National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Beijing 100023, PR China
| | - Cheng Qin
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100023, PR China; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100023, PR China; National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Beijing 100023, PR China
| | - Chen Lin
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100023, PR China; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100023, PR China; National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Beijing 100023, PR China
| | - Zeru Li
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100023, PR China; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100023, PR China; National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Beijing 100023, PR China
| | - Bangbo Zhao
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100023, PR China; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100023, PR China; National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Beijing 100023, PR China
| | - Tianyu Li
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100023, PR China; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100023, PR China; National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Beijing 100023, PR China
| | - Xiangyu Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100023, PR China; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100023, PR China; National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Beijing 100023, PR China
| | - Weibin Wang
- Department of General Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing 100023, PR China; Key Laboratory of Research in Pancreatic Tumor, Chinese Academy of Medical Sciences, Beijing 100023, PR China; National Science and Technology Key Infrastructure on Translational Medicine in Peking Union Medical College Hospital, Beijing 100023, PR China.
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Zhang L, Wang X, Yang X, Chi Y, Chu Y, Zhang Y, Gong Y, Wang F, Zhao Q, Zhao D. Genome Engineering of Primary and Pluripotent Stem Cell-Derived Hepatocytes for Modeling Liver Tumor Formation. BIOLOGY 2024; 13:684. [PMID: 39336111 PMCID: PMC11428634 DOI: 10.3390/biology13090684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/16/2024] [Revised: 08/20/2024] [Accepted: 08/27/2024] [Indexed: 09/30/2024]
Abstract
Genome editing has demonstrated its utility in generating isogenic cell-based disease models, enabling the precise introduction of genetic alterations into wild-type cells to mimic disease phenotypes and explore underlying mechanisms. However, its application in liver-related diseases has been limited by challenges in genetic modification of mature hepatocytes in a dish. Here, we conducted a systematic comparison of various methods for primary hepatocyte culture and gene delivery to achieve robust genome editing of hepatocytes ex vivo. Our efforts yielded editing efficiencies of up to 80% in primary murine hepatocytes cultured in monolayer and 20% in organoids. To model human hepatic tumorigenesis, we utilized hepatocytes differentiated from human pluripotent stem cells (hPSCs) as an alternative human hepatocyte source. We developed a series of cellular models by introducing various single or combined oncogenic alterations into hPSC-derived hepatocytes. Our findings demonstrated that distinct mutational patterns led to phenotypic variances, affecting both overgrowth and transcriptional profiles. Notably, we discovered that the PI3KCA E542K mutant, whether alone or in combination with exogenous c-MYC, significantly impaired hepatocyte functions and facilitated cancer metabolic reprogramming, highlighting the critical roles of these frequently mutated genes in driving liver neoplasia. In conclusion, our study demonstrates genome-engineered hepatocytes as valuable cellular models of hepatocarcinoma, providing insights into early tumorigenesis mechanisms.
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Affiliation(s)
- Lulu Zhang
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; (L.Z.); (Y.C.); (Y.C.); (Y.G.); (F.W.); (Q.Z.)
- University of Chinese Academy of Sciences, Beijing 101408, China
| | - Xunting Wang
- School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; (X.W.); (X.Y.); (Y.Z.)
| | - Xuelian Yang
- School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; (X.W.); (X.Y.); (Y.Z.)
| | - Yijia Chi
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; (L.Z.); (Y.C.); (Y.C.); (Y.G.); (F.W.); (Q.Z.)
- University of Chinese Academy of Sciences, Beijing 101408, China
| | - Yihang Chu
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; (L.Z.); (Y.C.); (Y.C.); (Y.G.); (F.W.); (Q.Z.)
- School of Life Science and Technology, Shanghai Tech University, Shanghai 201210, China
| | - Yi Zhang
- School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; (X.W.); (X.Y.); (Y.Z.)
| | - Yufan Gong
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; (L.Z.); (Y.C.); (Y.C.); (Y.G.); (F.W.); (Q.Z.)
- University of Chinese Academy of Sciences, Beijing 101408, China
| | - Fei Wang
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; (L.Z.); (Y.C.); (Y.C.); (Y.G.); (F.W.); (Q.Z.)
| | - Qian Zhao
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; (L.Z.); (Y.C.); (Y.C.); (Y.G.); (F.W.); (Q.Z.)
| | - Dongxin Zhao
- Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China; (L.Z.); (Y.C.); (Y.C.); (Y.G.); (F.W.); (Q.Z.)
- University of Chinese Academy of Sciences, Beijing 101408, China
- School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China; (X.W.); (X.Y.); (Y.Z.)
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Duan Z, Yang M, Yang J, Wu Z, Zhu Y, Jia Q, Ma X, Yin Y, Zheng J, Yang J, Jiang S, Hu L, Zhang J, Liu D, Huo Y, Yao L, Sun Y. AGFG1 increases cholesterol biosynthesis by disrupting intracellular cholesterol homeostasis to promote PDAC progression. Cancer Lett 2024; 598:217130. [PMID: 39089666 DOI: 10.1016/j.canlet.2024.217130] [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: 05/14/2024] [Revised: 07/01/2024] [Accepted: 07/17/2024] [Indexed: 08/04/2024]
Abstract
PURPOSE Cholesterol metabolism reprograming has been acknowledged as a novel feature of cancers. Pancreatic ductal adenocarcinoma (PDAC) is a cancer with a high demand of cholesterol for rapid growth. The underlying mechanism of how cholesterol metabolism homestasis are disturbed in PDAC is explored. EXPERIMENTAL DESIGN The relevance between PDAC and cholesterol was confirmed in TCGA database. The expression and clinical association were discovered in TCGA and GEO datasets. Knockdown and overexpression of AGFG1 was adopted to perform function studies. RNA sequencing, cholesterol detection, transmission electron microscope, co-immunoprecipitation, and immunofluorescence et al. were utilized to reveal the underlying mechanism. RESULTS AGFG1 was identified as one gene positively correlated with cholesterol metabolism in PDAC as revealed by bioinformatics analysis. AGFG1 expression was then found associated with poor prognosis in PDAC. AGFG1 knockdown led to decreased proliferation of tumor cells both in vitro and in vivo. By RNA sequencing, we found AGFG1 upregulated expression leads to enhanced intracellular cholesterol biosynthesis. AGFG1 knockdown suppressed cholesterol biosynthesis and an accumulation of cholesterol in the ER. Mechanistically, we confirmed that AGFG1 interacted with CAV1 to relocate cholesterol for the proceeding of cholesterol biosynthesis, therefore causing disorders in intracellular cholesterol metabolism. CONCLUSIONS Our study demonstrates the tumor-promoting role of AGFG1 by disturbing cholesterol metabolism homestasis in PDAC. Our study has present a new perspective on cancer therapeutic approach based on cholerstrol metabolism in PDAC.
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Affiliation(s)
- Zonghao Duan
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, PR China; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, PR China
| | - Minwei Yang
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, PR China
| | - Jian Yang
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, PR China; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, PR China; Department of General Surgery, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, PR China; Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100029, PR China
| | - Zheng Wu
- Department of Radiation Oncology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, PR China
| | - Yuheng Zhu
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, PR China; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, PR China
| | - Qinyuan Jia
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, PR China; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, PR China
| | - Xueshiyu Ma
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, PR China
| | - Yifan Yin
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, PR China
| | - Jiahao Zheng
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, PR China; State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, PR China
| | - Jianyu Yang
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, PR China
| | - Shuheng Jiang
- State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, PR China
| | - Lipeng Hu
- State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, PR China
| | - Junfeng Zhang
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, PR China; Department of General Surgery, Jiading District Central Hospital Affiliated Shanghai University of Medicine & Health Sciences, Shanghai, 201800, PR China
| | - Dejun Liu
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, PR China.
| | - Yanmiao Huo
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, PR China.
| | - Linli Yao
- State Key Laboratory of Systems Medicine for Cancer, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200240, PR China.
| | - Yongwei Sun
- Department of Biliary-Pancreatic Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, PR China.
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11
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Mao Y, Hu H. Establishment of advanced tumor organoids with emerging innovative technologies. Cancer Lett 2024; 598:217122. [PMID: 39029781 DOI: 10.1016/j.canlet.2024.217122] [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: 03/21/2024] [Revised: 06/21/2024] [Accepted: 07/12/2024] [Indexed: 07/21/2024]
Abstract
Tumor organoids have emerged as a crucial preclinical model for multiple cancer research. Their high establishment rates, stability, and ability to replicate key biological features of original tumor cells in vivo render them invaluable for exploring tumor molecular mechanisms, discovering potential anti-tumor drugs, and predicting clinical drug efficacy. Here, we review the establishment of tumor organoid models and provide an extensive overview of organoid culturing strategies. We also emphasize the significance of integrating cellular components of the tumor microenvironment and physicochemical factors in the organoid culturing system, highlighting the importance of artificial intelligence technology in advancing organoid construction. Moreover, we summarize recent advancements in utilizing organoid systems for novel anti-cancer drug screening and discuss promising trends for enhancing advanced organoids in next-generation disease modeling.
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Affiliation(s)
- Yunuo Mao
- The Key Laboratory of Experimental Teratology, Ministry of Education, Department of Systems Biomedicine, School of Basic Medical Sciences, Shandong University, Jinan, 250012, PR China
| | - Huili Hu
- The Key Laboratory of Experimental Teratology, Ministry of Education, Department of Systems Biomedicine, School of Basic Medical Sciences, Shandong University, Jinan, 250012, PR China.
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12
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Wu H, Fu M, Wu M, Cao Z, Zhang Q, Liu Z. Emerging mechanisms and promising approaches in pancreatic cancer metabolism. Cell Death Dis 2024; 15:553. [PMID: 39090116 PMCID: PMC11294586 DOI: 10.1038/s41419-024-06930-0] [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: 04/18/2024] [Revised: 07/17/2024] [Accepted: 07/22/2024] [Indexed: 08/04/2024]
Abstract
Pancreatic cancer is an aggressive cancer with a poor prognosis. Metabolic abnormalities are one of the hallmarks of pancreatic cancer, and pancreatic cancer cells can adapt to biosynthesis, energy intake, and redox needs through metabolic reprogramming to tolerate nutrient deficiency and hypoxic microenvironments. Pancreatic cancer cells can use glucose, amino acids, and lipids as energy to maintain malignant growth. Moreover, they also metabolically interact with cells in the tumour microenvironment to change cell fate, promote tumour progression, and even affect immune responses. Importantly, metabolic changes at the body level deserve more attention. Basic research and clinical trials based on targeted metabolic therapy or in combination with other treatments are in full swing. A more comprehensive and in-depth understanding of the metabolic regulation of pancreatic cancer cells will not only enrich the understanding of the mechanisms of disease progression but also provide inspiration for new diagnostic and therapeutic approaches.
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Affiliation(s)
- Hao Wu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Mengdi Fu
- Department of Clinical Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Mengwei Wu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Zhen Cao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Qiyao Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Ziwen Liu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
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13
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Fu Y, Tao J, Liu T, Liu Y, Qiu J, Su D, Wang R, Luo W, Cao Z, Weng G, Zhang T, Zhao Y. Unbiasedly decoding the tumor microenvironment with single-cell multiomics analysis in pancreatic cancer. Mol Cancer 2024; 23:140. [PMID: 38982491 PMCID: PMC11232163 DOI: 10.1186/s12943-024-02050-7] [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: 05/07/2024] [Accepted: 06/21/2024] [Indexed: 07/11/2024] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a poor prognosis and limited therapeutic options. Research on the tumor microenvironment (TME) of PDAC has propelled the development of immunotherapeutic and targeted therapeutic strategies with a promising future. The emergence of single-cell sequencing and mass spectrometry technologies, coupled with spatial omics, has collectively revealed the heterogeneity of the TME from a multiomics perspective, outlined the development trajectories of cell lineages, and revealed important functions of previously underrated myeloid cells and tumor stroma cells. Concurrently, these findings necessitated more refined annotations of biological functions at the cell cluster or single-cell level. Precise identification of all cell clusters is urgently needed to determine whether they have been investigated adequately and to identify target cell clusters with antitumor potential, design compatible treatment strategies, and determine treatment resistance. Here, we summarize recent research on the PDAC TME at the single-cell multiomics level, with an unbiased focus on the functions and potential classification bases of every cellular component within the TME, and look forward to the prospects of integrating single-cell multiomics data and retrospectively reusing bulk sequencing data, hoping to provide new insights into the PDAC TME.
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Affiliation(s)
- Yifan Fu
- General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
- 4+4 Medical Doctor Program, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Jinxin Tao
- General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Tao Liu
- General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Yueze Liu
- General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Jiangdong Qiu
- General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Dan Su
- General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Ruobing Wang
- General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Wenhao Luo
- General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Zhe Cao
- General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Guihu Weng
- General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China
| | - Taiping Zhang
- General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
- Clinical Immunology Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
| | - Yupei Zhao
- General Surgery Department, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.
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14
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Bose S, Shen X. The KRAS tour: Studying metabolic reprogramming in isogenic pancreatic cancer organoids. Cell Stem Cell 2024; 31:1-2. [PMID: 38181746 DOI: 10.1016/j.stem.2023.12.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2023] [Revised: 12/12/2023] [Accepted: 12/12/2023] [Indexed: 01/07/2024]
Abstract
Using an isogenic organoid platform to model pancreatic cancer, Duan et al. establish an important link between mutant KRAS and cholesterol metabolism and identify perhexiline maleate as a possible therapeutic to target this relationship.
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Affiliation(s)
- Shree Bose
- Department of Internal Medicine, University of Chicago, Chicago, IL, USA
| | - Xiling Shen
- Terasaki Institute for Biomedical Innovation, Los Angeles, CA, USA.
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