All-trans Retinoic Acid Sensitizes Epithelial Ovarian Cancer to PARP Inhibition after Exposure to Cisplatin.

ABSTRACT: Epithelial ovarian cancer (EOC) is the most lethal of gynecologic malignancies. The standard-of-care treatment for EOC is platinum-based chemotherapy such as cisplatin (CDDP). Notably, platinum-based chemotherapy induces resistance of EOC to PARP inhibition. However, therapeutic approaches targeting PARP inhibitor (PARPi) resistance remain to be explored. In this study, we show that all-trans retinoic acid (ATRA) reduces PARPi resistance-associated EOC cells induced by CDDP treatment. Clinically applicable ATRA suppressed the outgrowth of CDDP-treated EOC cells both in vitro and in vivo. Moreover, a CDDP treatment followed by niraparib maintenance therapy in combination with ATRA improved the survival of EOC-bearing mice. These phenotypes correlated with the PARPi-resistant EOC signature,

SUBMITTER: Mei B 

PROVIDER: S-EPMC11876957 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature