Targeting FEN1/EXO1 to enhance efficacy of PARP inhibition in triple-negative breast cancer.

ABSTRACT: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. The only targeted therapeutic approach that has emerged for early TNBC patients with BRCA-mutations (BRCA^MUT) are PARP inhibitors (PARPi). In combination, PARPi may benefit a larger cohort of TNBC patients. We used our previously identified 63-gene signature that was associated with PARPi response to identify candidate genes that could be therapeutic targets. We selected FEN1 for further investigation since its knockdown was associated with an increase in G2/M arrest, DNA damage, and apoptosis. We first tested LNT1, a FEN1/EXO1 inhibitor, in a panel of 10 TNBC cell lines. LNT1 sensitivity was identified predominantly in BRCA1-mutant/deficient cell lines. However, the combination of PARPi and LN

SUBMITTER: Frederick MI 

PROVIDER: S-EPMC11928819 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature