Abstract 3078: A pipeline for functional precision medicine in bone and soft tissue sarcoma organoids

Abstract Bone and soft tissue sarcomas span a spectrum of over one hundred histologic subtypes. Developing clinical trials and identifying effective therapies remains a challenge given the rarity of these tumors and scarcity of available tumor models. Patient-derived tumor organoids (PDTOs) are representative of the native physiology of tumors across an array of malignancies (Phan et al, 2019; Al Shihabi et al, 2021). For rare tumors such as bone and soft tissue sarcomas, PDTOs could constitute an important tool to better understand the biology of the disease and identify treatment options. Here, we present the pipeline we have established at UCLA to systematically procure tissue, develop and characterize individualized sarcoma PDTOs, and identify tumor sensitivities using high-throughput drug screening. We have collected tumor specimens from 114 patients diagnosed with sarcomas, representing more than 30 distinct subtypes of soft tissue and bone tumors. We have established suitable conditions to generate organoids from over 100 samples collected from needle biopsies, tumor resections, and metastasectomies, including soft tissue sarcomas (liposarcoma, undifferentiated pleomorphic sarcoma, leiomyosarcoma, etc.) and bone sarcomas (chondrosarcoma, osteosarcoma, Ewing sarcoma, etc.). We take advantage of our mini-ring technology to generate PDTOs in a format compatible with high-throughput drug screening (Phan et al, 2019; Nguyen et al, 2020). Our results highlight tumor-specific drug susceptibilities to chemotherapeutics, targeted agents, and combination therapies, generating results within a week from surgery. We will show how several of the organoid response patterns we identified transcend cancer subtype and patient characteristics. Our findings support the feasibility of rapidly generating individualized organoid models from bone and soft tissue sarcomas to facilitate biological interrogations and investigate response to treatment. Direct testing of PDTOs derived from clinical specimens can provide timely, actionable information for functional precision medicine approaches with the potential to improve patient outcomes. Citation Format: Ahmad Al Shihabi, Peyton J. Tebon, Jomjit Chantharasamee, Huyen T. Nguyen, Sara Sartini, Ardalan Davarifar, Nasrin Tavanaie, Scott D. Nelson, Noah Federman, Jane Yanagawa, Alice Soragni. A pipeline for functional precision medicine in bone and soft tissue sarcoma organoids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3078.