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患者来源的直肠癌类器官——在基础和转化癌症研究中的应用

Patient-derived rectal cancer organoids-applications in basic and translational cancer research.

作者信息

Yan Yumeng, Cheong Io Hong, Chen Peizhan, Li Xiaoguang, Wang Xianli, Wang Hui

机构信息

School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

State Key Laboratory of Oncogenes and Related Genes, Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Front Oncol. 2022 Jul 26;12:922430. doi: 10.3389/fonc.2022.922430. eCollection 2022.

DOI:10.3389/fonc.2022.922430
PMID:35957894
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9360321/
Abstract

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and among the leading causes of death in both men and women. Rectal cancer (RC) is particularly challenging compared with colon cancer as the treatment after diagnosis of RC is more complex on account of its narrow anatomical location in the pelvis adjacent to the urogenital organs. More and more existing studies have begun to refine the research on RC and colon cancer separately. Early diagnosis and multiple treatment strategies optimize outcomes for individual patients. However, the need for more accurate and precise models to facilitate RC research is underscored due to the heterogeneity of clinical response and morbidity interrelated with radical surgery. Organoids generated from biopsies of patients have developed as powerful models to recapitulate many aspects of their primary tissue, consisting of 3-D self-organizing structures, which shed great light on the applications in both biomedical and clinical research. As the preclinical research models for RC are usually confused with colon cancer, research on patient-derived RC organoid models enable personalized analysis of cancer pathobiology, organizational function, and tumor initiation and progression. In this review, we discuss the various applications of patient-derived RC organoids over the past two years in basic cancer biology and clinical translation, including sequencing analysis, drug screening, precision therapy practice, tumor microenvironment studies, and genetic engineering opportunities.

摘要

结直肠癌(CRC)是最常被诊断出的癌症之一,也是男性和女性主要的死亡原因之一。与结肠癌相比,直肠癌(RC)的治疗尤其具有挑战性,因为RC诊断后的治疗因其在骨盆中靠近泌尿生殖器官的狭窄解剖位置而更为复杂。越来越多的现有研究开始分别细化对RC和结肠癌的研究。早期诊断和多种治疗策略可优化个体患者的治疗效果。然而,由于临床反应的异质性以及与根治性手术相关的发病率,强调需要更准确和精确的模型来促进RC研究。从患者活检组织中生成的类器官已发展成为强大的模型,能够重现其原发组织的许多方面,由三维自组织结构组成,这为生物医学和临床研究的应用提供了重要启示。由于RC的临床前研究模型通常与结肠癌混淆,对患者来源的RC类器官模型的研究能够对癌症病理生物学、组织功能以及肿瘤的发生和发展进行个性化分析。在本综述中,我们讨论了过去两年患者来源的RC类器官在基础癌症生物学和临床转化中的各种应用,包括测序分析、药物筛选、精准治疗实践、肿瘤微环境研究以及基因工程机会。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3277/9360321/5bf7a907856f/fonc-12-922430-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3277/9360321/5bf7a907856f/fonc-12-922430-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3277/9360321/5bf7a907856f/fonc-12-922430-g001.jpg

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Cancer Res. 2022 Jun 15;82(12):2298-2312. doi: 10.1158/0008-5472.CAN-21-4128.
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ACO/ARO/AIO-21 - Capecitabine-based chemoradiotherapy in combination with the IL-1 receptor antagonist anakinra for rectal cancer Patients: A phase I trial of the German rectal cancer study group.ACO/ARO/AIO-21 - 卡培他滨联合白细胞介素-1受体拮抗剂阿那白滞素用于直肠癌患者的放化疗:德国直肠癌研究组的一项I期试验
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Predicting response to neoadjuvant chemoradiotherapy in rectal cancer: from biomarkers to tumor models.
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