Bivalent chromatin as a therapeutic target in cancer: An in silico predictive approach for combining epigenetic drugs.

ABSTRACT: Tumour cell heterogeneity is a major barrier for efficient design of targeted anti-cancer therapies. A diverse distribution of phenotypically distinct tumour-cell subpopulations prior to drug treatment predisposes to non-uniform responses, leading to the elimination of sensitive cancer cells whilst leaving resistant subpopulations unharmed. Few strategies have been proposed for quantifying the variability associated to individual cancer-cell heterogeneity and minimizing its undesirable impact on clinical outcomes. Here, we report a computational approach that allows the rational design of combinatorial therapies involving epigenetic drugs against chromatin modifiers. We have formulated a stochastic model of a bivalent transcription factor that allows us to characterise three different qual

SUBMITTER: Alarcon T 

PROVIDER: S-EPMC8248646 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature