Abstract

Leveraging Patient-derived Tumor Organoids For Precision Medicine

Alice Soragni, Assistant Professor, University of California Los Angeles

Patient-derived tumor organoids (PDTOs) are representative of the histopathology and physiological behavior of tumors. They are clinically relevant, tractable ex vivo models that can be quickly established from tumor biopsies and surgical samples. There is increasing interest in leveraging tumor organoids for drug development and personalized medicine applications for their ability to maintain principal features of the tumor they originate from, including drug response. PDTOs are particularly important to model rare tumors which often completely lack experimental models. We routinely establish organoids from a spectrum of tumors, including rare ovarian and peritoneal cancers (Phan et al, Communications Biology, 2019), benign tumors such as cutaneous neurofibromas (Nguyen et al, Cell Reports Methods, 2024), indolent bone cancers (Al Shihabi et al, Science Advances, 2022) and aggressive sarcomas (Al Shihabi et al, in press, 2024). We have developed a unique organoid screening platform that uses a modified geometry to seed or bioprint cells in a robust, high throughput and automation-compatible format that bypasses the need for any cell sorting, passaging or in vitro expansion. Our short screening timeline, with results available within one week from surgery, is compatible with therapeutic decision making. Overall, we have been able to identify unique drug responses to both fast and slow-growing cancers, including for tumors that are recalcitrant or impossible to grow as patient-derived xenografts. In a pilot study of PDTOs established from over 120 sarcomas, a family of rare tumors arising from bone or soft tissue, we demonstrated how PDTO drug screening provides sensitivity information that correlates with clinical features yielding actionable information for treatment guidance (Al Shihabi et al, in press, 2024). Importantly, sarcoma organoid responses complemented genetic sequencing and mirrored patient outcomes, leading to the launch of a clinical trial to test PDTO use in osteosarcoma (An Organoid-based Functional Precision Medicine Trial in Osteosarcoma: PREMOST, NCT06064682).