Unmatched Cell Line Collections Are Not Optimal for Identification of PARP Inhibitor Response and Drug Synergies.

ABSTRACT: PARP inhibitors show great efficacy in BRCA1/2-mutated patients, but many preclinical studies, including combination therapies, fail to translate clinically, likely due to the limitations of preclinical models. This brief report aimed to identify appropriate cell line models to investigate PARP inhibitor sensitivity and synergies. An in silico study of cell line collections was performed to assess the correlation between BRCA1/2 mutations and sensitivity to PARP inhibitor monotherapy or with platinum-based chemotherapy. Subsequently, we characterised an isogenic model containing Brca1 and Brca2 mutations and investigated treatment response. Using cell line collections, BRCA1- and BRCA2-altered cell lines were not associated with increased sensitivity to PARP inhibitors. Other factors, incl

SUBMITTER: Phan Z 

PROVIDER: S-EPMC12451393 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature