The synergistic action of HDAC inhibitor with cisplatin impedes survival and proliferation of drug-tolerant persister in gastric and liver cancer cells.

ABSTRACT: Acquired therapy resistance is a dynamic process associated with early epigenetic modifications reshaping gene transcription across multiple cellular pathways, ultimately giving rise to drug-tolerant persister (DTP) cells. Unraveling the mechanisms that sustain DTP cell survival and drive their evolution into stable drug-resistant cells (DRC) is crucial for developing targeted therapies. Cisplatin-tolerant and cisplatin-resistant models were established using liver and gastric cancer cell lines for the first time to explore these mechanisms. Our investigation centered on the distinct epigenetic landscapes of DTP and DRC cells following cisplatin exposure. RNA sequencing revealed that DTP cells exhibit downregulation of pathways involved in cell cycle regulation, DNA replication, transcript

SUBMITTER: Singh A 

PROVIDER: S-EPMC12506338 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature