Phenotypic heterogeneity and evolution of melanoma cells associated with targeted therapy resistance.

ABSTRACT: Phenotypic plasticity is associated with non-genetic drug tolerance in several cancers. Such plasticity can arise from chromatin remodeling, transcriptomic reprogramming, and/or protein signaling rewiring, and is characterized as a cell state transition in response to molecular or physical perturbations. This, in turn, can confound interpretations of drug responses and resistance development. Using BRAF-mutant melanoma cell lines as the prototype, we report on a joint theoretical and experimental investigation of the cell-state transition dynamics associated with BRAF inhibitor drug tolerance. Thermodynamically motivated surprisal analysis of transcriptome data was used to treat the cell population as an entropy maximizing system under the influence of time-dependent constraints. This perm

SUBMITTER: Su Y 

PROVIDER: S-EPMC6576794 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature