Ex vivo drug sensitivity testing predicts treatment outcomes in advanced ovarian cancer

Effective clinical management of advanced epithelial ovarian cancer (EOC) remains a major challenge, with most patients relapsing despite standard therapies, emphasizing the need for individualized treatment strategies and predictive approaches. Here, functional ex vivo drug testing may provide a translational approach to match patients with effective, personalized therapies based on drug sensitivity. We present DRUGSENS, a scalable and clinically adaptable ex vivo drug response screening platform that enables quantitative assessment of single-cell, on-target effects in both cultured cell lines and patient-derived samples. DRUGSENS supports high-resolution analysis of cellular responses to individual therapeutic agents and clinically relevant drug combinations, with the potential to inform personalized treatment strategies across diverse tumor types and tissue contexts. This semi-automated ex vivo assay integrates immunofluorescence-based confocal imaging with computational analysis using QuPath, Fiji, and a developed DRUGSENS R package. We successfully generated individualized drug sensitivity profiles for 21 samples derived from 17 patients across both chemotherapy-naive and relapsed disease states, achieving a 100% success rate of culture efficiency and generating individualized drug profiles within a 10-day turnaround time. Notably, most resistant samples showed poor response to multiple agents, suggesting a multidrug-resistant phenotype. Ex vivo drug responses significantly correlated with clinical outcomes, including progression-free and overall survival. In conclusion, DRUGSENS platform enables rapid, clinically relevant functional profiling of therapeutic responses in EOC and represents a valuable tool to guide treatment recommendations and suggest drug prioritization for clinical application.