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使用患者来源的类器官预测结直肠癌治疗反应的疗效

The Efficacy of Using Patient-Derived Organoids to Predict Treatment Response in Colorectal Cancer.

作者信息

Su Chang, Olsen Kelly A, Bond Catherine E, Whitehall Vicki L J

机构信息

Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Herston 4006, Australia.

Faculty of Medicine, The University of Queensland, Herston 4006, Australia.

出版信息

Cancers (Basel). 2023 Jan 28;15(3):805. doi: 10.3390/cancers15030805.

DOI:10.3390/cancers15030805
PMID:36765763
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9913532/
Abstract

Colorectal cancer is an important cause of morbidity and mortality worldwide. The current treatment landscape includes chemotherapy, targeted therapy, immunotherapy, radiotherapy, and surgery. A key challenge to improving patient outcomes is the significant inter-patient heterogeneity in treatment response. Tumour organoids derived from the patients' tumours via surgically resected or endoscopically biopsied tissue, have emerged as promising models for personalised medicine. This review synthesises the findings, to date, of studies which have explored the efficacy of ex vivo organoid sensitivity testing for predicting treatment response. Most studies have focused on predicting the response to standard-of-care radiotherapy and chemotherapy options. There is strong evidence to support organoid sensitivity testing of ionising radiation, 5-fluorouracil, and irinotecan, and to a lesser extent, oxaliplatin and TAS-102. Fewer studies have used organoids to identify patients who are likely to benefit from novel treatment options that otherwise remain in clinical trials. This review also summarises recent advancements in organoid culture to include non-epithelial components of the tumour microenvironment, to allow testing of immunotherapy and certain targeted therapy options. Overall, further prospective trials will support the implementation of organoid-based personalised medicine for colorectal cancer patients in the future.

摘要

结直肠癌是全球发病和死亡的重要原因。当前的治疗方式包括化疗、靶向治疗、免疫治疗、放疗和手术。改善患者治疗效果的一个关键挑战是患者间治疗反应存在显著异质性。通过手术切除或内镜活检组织从患者肿瘤中获取的肿瘤类器官,已成为个性化医疗的有前景的模型。这篇综述总结了迄今为止探索体外类器官敏感性测试预测治疗反应疗效的研究结果。大多数研究集中于预测对标准护理放疗和化疗方案的反应。有强有力的证据支持对电离辐射、5-氟尿嘧啶和伊立替康进行类器官敏感性测试,对奥沙利铂和TAS-102的支持力度较小。较少有研究使用类器官来识别可能从仍处于临床试验阶段的新型治疗方案中获益的患者。这篇综述还总结了类器官培养的最新进展,包括肿瘤微环境的非上皮成分,以允许对免疫治疗和某些靶向治疗方案进行测试。总体而言,进一步的前瞻性试验将支持未来为结直肠癌患者实施基于类器官的个性化医疗。

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本文引用的文献

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Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.转移性结直肠癌:ESMO 诊断、治疗及随访临床实践指南
Ann Oncol. 2023 Jan;34(1):10-32. doi: 10.1016/j.annonc.2022.10.003. Epub 2022 Oct 25.
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Culture media composition influences patient-derived organoid ability to predict therapeutic responses in gastrointestinal cancers.培养介质组成影响患者来源的类器官在胃肠道癌症中预测治疗反应的能力。
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Patient-derived tumor organoids predict responses to irinotecan-based neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer.患者来源的肿瘤类器官可预测局部晚期直肠癌患者对基于伊立替康的新辅助放化疗的反应。
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Reactions of cisplatin and oxaliplatin with penicillin G: implications for drug inactivation and biological activity.顺铂和奥沙利铂与青霉素 G 的反应:对药物失活和生物活性的影响。
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Patient-Derived Organoids from Colorectal Cancer with Paired Liver Metastasis Reveal Tumor Heterogeneity and Predict Response to Chemotherapy.结直肠癌伴配对肝转移患者衍生类器官揭示肿瘤异质性并预测化疗反应。
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3-Dimensional Model to Study Apoptosis Induction of Activated Natural Killer Cells Conditioned Medium Using Patient-Derived Colorectal Cancer Organoids.利用患者来源的结直肠癌类器官建立三维模型以研究活化自然杀伤细胞条件培养基诱导的细胞凋亡
Front Cell Dev Biol. 2022 May 26;10:895284. doi: 10.3389/fcell.2022.895284. eCollection 2022.
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Patient-Derived Organoid Serves as a Platform for Personalized Chemotherapy in Advanced Colorectal Cancer Patients.患者来源的类器官作为晚期结直肠癌患者个性化化疗的平台。
Front Oncol. 2022 Jun 1;12:883437. doi: 10.3389/fonc.2022.883437. eCollection 2022.
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