In high-grade serous ovarian cancer (HGSC), BRCA2 mutations impair DNA repair via homologous recombination (HR), creating initial sensitivity to platinum-based chemotherapy and PARP inhibitors (PARPi) (1). Resistance often emerges through secondary BRCA2 mutations that restore HR (2). This functional change is detectable via RAD51 foci formation, a widely used marker of HR competence. Studying this evolution is key to understanding and overcoming acquired drug resistance.
The PEO series uniquely models this trajectory. PEO1, PEO4, and PEO6 were derived from the same patient at different treatment stages. PEO1-OR, selected in vitro for olaparib resistance, extends the series by providing a model of acquired PARPi resistance, while PEO1-CDDP, an in vitro cisplatin-selected derivative of PEO1, adds a complementary platinum-resistant model. Together, these lines offer matched, mechanistically distinct models for investigating DNA repair mechanisms, drug resistance pathways, and response prediction in ovarian cancer.
