PARP inhibitor augments anti-tumor efficacy of DNMT inhibitor by inducing senescence in cholangiocarcinoma.

ABSTRACT: Cholangiocarcinoma (CCA) is an aggressive, heterogeneous malignancy with limited effective treatment options. One of the key epigenetic dysregulations in CCA is aberrant DNA hypermethylation, suggesting that targeted DNA methylation is a promising therapeutic strategy for this disease. However, there is still limited information on how effective DNA demethylating agents are in the treatment of CCA in the clinical setting, and further studies are urgently needed to evaluate their potential benefits. Here, we established four patient-derived CCA cell lines and demonstrated that the DNA methyltransferase (DMNT) inhibitors decitabine and azacitidine had minimal effects on inhibiting CCA proliferation. A combinatorial drug screen identified PARP inhibitors as sensitizers that synergistically en

SUBMITTER: Wang P 

PROVIDER: S-EPMC12160928 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature