Interplay of replication stress response and immune microenvironment in high-grade serous ovarian cancer.

ABSTRACT: High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy. Therapeutic options remain limited for patients lacking predictive biomarkers, particularly those with BRCA wild-type tumors or those who have acquired resistance to both PARP inhibitors and platinum-based chemotherapy. Replication stress, TP53 mutations, and genomic instability characterize HGSOC. The cellular response to replication stress is primarily mediated by checkpoint kinases; however, this mechanism is frequently impaired in tumor cells. Consequently, cancer cells become increasingly dependent on the replication stress response (RSR) pathway for survival, and susceptible to therapies targeting the ATR-CHK1-WEE1 axis-a key regulator of genomic integrity. Inhibition of these checkpoint kinases can

SUBMITTER: Venegas L 

PROVIDER: S-EPMC12446242 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature