Ascites-Derived Organoids for Prediction of Treatment Response and Clinical Management in Ovarian Cancer
Arias-Diaz, A. E.; Fernandez Diaz, N.; Perez-Beliz, E.; Otero-Alen, M.; Vilar, A.; Diaz, E.; Moreno-Bueno, G.; Dominguez-Medina, E.; Bernardez, B.; Lopez-Lopez, R.; Curiel, T.; Abal, M.
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High grade serous ovarian cancer patients initially respond to platinum-based chemotherapy, but usually relapse within two years and ultimately develop therapy resistance. Management of response and effective clinical decisions are currently based on unspecific biomarkers and limited imaging techniques, illustrating the clear clinical need for reliable predictors of response. In this work, we evaluated the performance of patient-derived organoids generated from ascitic fluid and functionally tested in parallel to the patients clinical course, in the prediction of treatment response, and guiding clinical decision-making in a patient-specific manner. Ascites derived organoids reliably recapitulated the histological and molecular features of a paradigmatic HGSOC patient with an apparent dissociated response, and demonstrated chemoresistance months before laparoscopy confirmed persistent inoperable disease with poor pathological response. Drug screening identified alternative therapeutic options, while multi-omics provided additional insights into the tumor-specific biological features, to assist in the personalized clinical management in ovarian cancer.
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