Increased efficacy of PARP inhibitors against cisplatin-sensitive and -resistant ovarian cancer cells mediated via ATR and ATM inhibition.

ABSTRACT: PARP inhibitors (PARPi) are approved for the treatment of platinum-based therapy-responsive ovarian cancer. However, this severely restricts their therapeutic potential, since there is only limited knowledge on the efficacy of PARPi in platinum drug-resistant ovarian cancer cells. Here, we studied three approved PARPi, niraparib, olaparib, and rucaparib in three ovarian cancer cell lines and their cisplatin-resistant sublines. Complex response profiles demonstrated that cisplatin resistance was not consistently associated with cross-resistance to PARPi. The combination of PARPi with inhibitors of relevant DNA damage response kinases which are potentially involved in PARPi resistance, such as ATR, ATM, CHK1, and WEE1 again resulted in complex activity patterns, but also identified ATR and A

SUBMITTER: Konig P 

PROVIDER: S-EPMC12501025 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature