Establishment of HGSOC-derived organoids for modeling therapeutic response
Molly Udaskin1, Nikolina Radulovich1, Quan Li1, Kevin CJ Nixon1, Irene Xie1, Pamela Soberanis Pina1, Lisa Wang1, Alhareth Azaizeh1, Robert Rottapel1, Ming-Sound Tsao1,2, Amit Oza1, Stephanie Lheureux1.
1Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada; 2Department of Laboratory Medicine and Pathology , University of Toronto, Toronto, ON, Canada
High-grade serous ovarian carcinoma (HGSOC) presents treatment challenges due to its aggressiveness and late diagnosis. Despite progress in surgery and targeted therapies, addressing its complex genetic makeup remains crucial for better outcomes. Resistance to standard treatments like platinum-based chemotherapy or PARP inhibitor further complicates management. Precision oncology, utilizing comprehensive models incorporating patient tumor characteristics, is vital for predicting responses and developing effective treatments. Patient-derived organoids (PDOs) show promise as advanced in vitro models for clinical use. We have successfully established long-term organoids from various HGSOC specimens, sourced from pleural fluids, surgical resections, and patient-derived xenografts. These HGSOC models are accompanied by patient information, including drug response data. Furthermore, our HGSOC organoids faithfully maintain the histological architecture, gene expression profiles, and genomic landscape of the original tumors. We have demonstrated that the drug response observed in PDO models correlates with the clinical response of patients. Moreover, through high-throughput screening, we identified compounds that synergize with PARP inhibitors to combat drug resistance. Our work highlights the crucial role of HGSOC-derived organoid models in enhancing our comprehension of HGSOC cancer biology and in applying personalized medicine approaches for addressing this illness.
Princess Margaret Cancer Foundation. OvCAN Priority 1: Research Models.