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Studying the Role of Chromosomal Instability (CIN) in GI Cancers Using Patient-derived Organoids

Journal

JOURNAL OF MOLECULAR BIOLOGY
Volume 434, Issue 3, Pages -

Publisher

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jmb.2021.167256

Keywords

gastrointestinal cancers; tumor organoids; chromosomal instability (CIN); carcinogenesis; intratumoral heterogeneity (ITH)

Funding

  1. Department of Science and Technology (DST) (Science & Engineering Research Board (SERB)) [CRG/2020/002563]
  2. Indian Institute of Science Education and Research (IISER) , Pune
  3. UGC, New Delhi
  4. IISER Pune

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Chromosomal instability (CIN) is associated with gastrointestinal (GI) tract cancers, and organoids provide a more realistic model to study the interaction between tumor cells and the tissue microenvironment and its impact on chromosomal stability.
Chromosomal instability (CIN) is associated with the initiation and progression of gastrointestinal (GI) tract cancers. Cancers of the GI tract are typically characterized by altered chromosome numbers. While the dynamics of CIN have been extensively characterized in 2D monolayer cell cultures derived from GI tumors, the tumor microenvironment and 3D tumor architecture also contribute to the progression of CIN, which is not captured in 2D cell culture systems. To overcome these limitations, self-organizing cellular structures that retain organ-specific 3D architecture, namely organoids, have been derived from various tissues of the GI tract. Organoids derived from normal tissue and patient tumors serve as a useful paradigm to study the crosstalk between tumor cells in the context of a tissue microenvironment and its impact on chromosomal stability. Such a paradigm, therefore, has a considerable advantage over 2D cell culture systems in drug screening and personalized medicine. Here, we review the importance of patient-derived tumor organoids (PDTOs) as a model to study CIN in cancers of the GI tract.(c) 2021 Elsevier Ltd. All rights reserved.

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