Heterogeneity of Ex Vivo Tumor Responses in Ovarian Cancer Tissues

BACKGROUND: Advanced-stage ovarian cancers exhibit significant variability in responses to standard chemotherapy ranging from platinum-refractory to platinum-sensitive cancers. While genomic testing reveals tissue heterogeneity, it rarely provides actionable data for guiding therapy. AIMS: To evaluate the heterogeneity of ex vivo drug responses in primary ovarian cancer tissues using a functional profiling platform, and to assess the platform's potential for guiding personalized therapy selection within current clinical practice. METHODS AND RESULTS: values, calculated using the ratio of upper and lower interdecile values. Seventeen ovarian cancer tissues were processed and exposed to NCCN-recommended drugs and drug combinations. Drug efficacy demonstrated significant interpatient heterogeneity (p < 0.001). Carboplatin and paclitaxel alone exhibited moderate heterogeneity (54-fold and 42-fold difference), while their combination showed higher heterogeneity (3880-fold difference), suggesting synergy in certain samples but not in others. Gemcitabine exhibited the highest single-agent heterogeneity across the cohort (1504-fold difference), whereas doxorubicin and olaparib demonstrated more consistent responses but limited efficacy in many samples (20-fold and 16-fold difference). CONCLUSION: These findings align with the clinically observed variability in patient responses, highlighting the platform's potential to optimize therapy selection and support patient-centric care within the standard of care for ovarian cancer patients.