Colorectal cancer cells possess an equipotent capacity to enter a developmental pausing-like state to survive chemotherapy

2 Datasets 1 Publication

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Dataset ID	Description	Technology	Samples
EGAD00001006847	None	Illumina HiSeq 2500	12
EGAD00001006849	Cancer cells enter a reversible drug tolerant persister (DTP) state to evade death from both chemotherapies and targeted agents. It is increasingly appreciated that the DTP state is an important driver of therapy failure and tumor relapse. We combined cellular barcoding and mathematical modeling in patient-derived colorectal cancer xenograft models to identify and characterize the cancer cells capable of generating DTPs in response to standard-of-care chemotherapy. Barcode analysis revealed no loss in clonal complexity of tumors that entered the DTP state and recurred following treatment cessation. Our data fits a mathematical model in which all cancer cells, and not a small subpopulation, possess an equipotent capacity to enter the DTP state. Mechanistically, we determined that DTPs display remarkable transcriptional and functional similarities to diapause, a reversible state of suspended embryonic development triggered by unfavorable environmental conditions. Our study provides new insights into how cancer cells use a developmentally conserved mechanism to drive the DTP state pointing to novel therapeutic opportunities to target diapause-like DTPs.	Illumina HiSeq 2500	12

Publications	Citations
Colorectal Cancer Cells Enter a Diapause-like DTP State to Survive Chemotherapy. Rehman SK, Haynes J, Collignon E, Brown KR, Wang Y, Nixon AML, Bruce JP, Wintersinger JA, Singh Mer A, Lo EBL, Leung C, Lima-Fernandes E, Pedley NM, Soares F, McGibbon S, He HH, Pollet A, Pugh TJ, Haibe-Kains B, Morris Q, Ramalho-Santos M, Goyal S, Moffat J, O'Brien CA. Cell 184: 2021 226-242.e21	156