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

Study ID Alternative Stable ID Type
EGAS00001004773 Cancer Genomics

Study Description

Study Datasets 2 dataset.

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Dataset ID Description Technology Samples
EGAD00001006847 NA 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

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