Longitudinal Prediction of Drug Response in High-Grade Serous Ovarian Cancer Organoid Cultures Aligning with Clinical Responses

Abstract

ABSTRACTHigh-grade serous ovarian cancer (HGSOC) ranks among the most aggressive gynecological malignancies. Its high mortality stems from frequent recurrence post-primary treatments and development of platinum resistance. Since, traditional drug development via animal models is time-consuming and lacks reproducibility, in precision cancer medicine, primary patient-derived organoids (PDOs) offer a solution by replicating disease pathophysiology and expediting drug screening. We developed an expandable HGSOC organoid platform for rapid drug screening and resistance testing. Our study aimed to validate the stability of seven PDO pairs in predicting drug responses over time. Organoids underwent low- and high-passage drug screenings over nine months, involving 21 conventional and FDA-approved drugs and proteomic analyses. Comparison of in vitro outcomes with clinical data confirmed the platform’s predictive capacity. Notably, a PDO with BRCA1 mutation exhibited resistance to Carboplatin and PARP inhibitors, highlighting organoid models’ clinical relevance for novel targeted therapies such as the Peptidylprolyl Cis/Trans Isomerase, NIMA-Interacting 1 (Pin1), a valuable target for HGSOC patients.