4.4 Review

Emerging Prospects for the Study of Colorectal Cancer Stem Cells using Patient-derived Organoids

期刊

CURRENT CANCER DRUG TARGETS
卷 22, 期 3, 页码 195-208

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BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/1568009622666220117124546

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Colorectal cancer; cancer stem cells; tumor microenvironment; patient-derived organoids; personalized medicine; LGR5

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This review summarizes the application of human colorectal cancer patient-derived organoids (PDOs) in the study of cancer stem cells (CSCs) and the cancer stem cell niche. It focuses on the relevance of PDOs in understanding CSC-related signaling, interactions between CSCs and the tumor microenvironment, and the modeling of CSC-driven resistance to therapies.
Human colorectal cancer (CRC) patient-derived organoids (PDOs) are a powerful ex vivo platform to directly assess the impact of molecular alterations and therapies on tumor cell proliferation, differentiation, response to chemotherapy, tumor-microenvironment interactions, and other facets of CRC biology. Next-generation sequencing studies have demonstrated that CRC is a highly heterogeneous disease with multiple distinct subtypes. PDOs are a promising new tool to study CRC due to their ability to accurately recapitulate their source tumor and thus reproduce this heterogeneity. This review summarizes the state-of-the-art for CRC PDOs in the study of cancer stem cells (CSCs) and the cancer stem cell niche. Areas of focus include the relevance of PDOs to understanding CSC-related paracrine signaling, identifying interactions between CSCs and the tumor microenvironment, and modeling CSC-driven resistance to chemotherapies and targeted therapies. Finally, we summarize current findings regarding the identification and verification of CSC targets using PDOs and their potential use in personalized medicine.

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