An in vitro model of tumor heterogeneity resolves genetic, epigenetic, and stochastic sources of cell state variability.

ABSTRACT: Tumor heterogeneity is a primary cause of treatment failure and acquired resistance in cancer patients. Even in cancers driven by a single mutated oncogene, variability in response to targeted therapies is well known. The existence of additional genomic alterations among tumor cells can only partially explain this variability. As such, nongenetic factors are increasingly seen as critical contributors to tumor relapse and acquired resistance in cancer. Here, we show that both genetic and nongenetic factors contribute to targeted drug response variability in an experimental model of tumor heterogeneity. We observe significant variability to epidermal growth factor receptor (EGFR) inhibition among and within multiple versions and clonal sublines of PC9, a commonly used EGFR mutant nonsmall ce

SUBMITTER: Hayford CE 

PROVIDER: S-EPMC8195356 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature