Integrating multiscale mathematical modeling and multidimensional data reveals the effects of epigenetic instability on acquired drug resistance in cancer.

ABSTRACT: Biological and dynamic mechanisms by which Drug-tolerant persister (DTP) cells contribute to the development of acquired drug resistance have not been fully elucidated. Here, by integrating multidimensional data from drug-treated PC9 cells, we developed a novel multiscale mathematical model from an evolutionary perspective that encompasses epigenetic and cellular population dynamics. By coupling stochastic simulation with quantitative analysis, we identified epigenetic instability as the most prominent kinetic feature related to the emergence of DTP cell subpopulations and the effectiveness of intermittent treatment. Moreover, we revealed the optimal schedule for intermittent treatment, including the optimal area for therapeutic time and drug holidays. By leveraging single-cell RNA-seq dat

SUBMITTER: Wang S 

PROVIDER: S-EPMC11835379 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature