PLK1 or WEE1 inhibition targets homologous recombination repair proficiency in BRCA1/2 wild-type high-grade serous ovarian cancer.

ABSTRACT: High-grade serous ovarian cancer (HGSOC) is a poor prognostic disease, especially in BRCA1/2 wild-type (BRCA-WT) patients with homologous recombination (HR) proficiency. These patients often show limited response to both platinum-based chemotherapy and PARP inhibitors. HR and non-homologous end joining (NHEJ) are the two major DNA double-strand break (DSB) repair pathways. HR is a precise repair mechanism for DSBs but is limited to S and G2 phases. In contrast, NHEJ functions more broadly throughout the cell cycle, including G1. We investigated whether inhibiting the G2/M checkpoint kinases PLK1 or WEE1 individually could disrupt mitotic control and expose therapeutic vulnerabilities in BRCA-WT/HR-proficient HGSOC cells. We evaluated cell cycle-targeted strategies to overcome HR-proficient

SUBMITTER: Xi Q 

PROVIDER: S-EPMC12727844 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature