An Organoid-based Functional Precision Medicine Trial in Osteosarcoma (PREMOST)

Alice Soragni, PhD shares information about PREMOST: an organoid-based functional PREcision Medicine trial in OSTeosarcoma (NCT06064682), a clinical trial that is studying the feasibility of using organoids for predicting drug response and guiding therapy in osteosarcoma.Patient-derived tumor organoids (PDTOs) are lab-grown replicas of tumors that closely resemble the original cancer in both structure and behavior. These models can be rapidly created from small samples obtained during biopsies or surgeries, allowing us to test their responses to different drugs in the lab. This makes them highly valuable for developing personalized treatment strategies, particularly in light of a growing body of evidence showing how PDTOs can in many cases accurately mimic clinical responses. The Soragni Lab has developed a unique platform to grow these organoids efficiently from osteosarcoma surgical samples. They can create these three-dimensional avatars without needing complicated cell sorting or lengthy lab procedures. This means they can start testing drugs and get results within a week of the surgery, a turnaround that is rapid enough to potentially be used in the future to help guide treatment decisions In a pilot study, they found that testing drugs on these organoids provided insights that closely matched the patients' actual clinical outcomes. Osteosarcoma organoids with low viability after neoadjuvant chemotherapy matched patients who experienced higher tumor cell death (necrosis) after treatment and long-term disease status. The lab also investigated responses of PDTOs from advanced, recurrent, and metastatic sarcomas and found that the viability of these organoids in the lab correlated with the time to the next treatment in patients. The data suggests that osteosarcoma organoids could help predict how well some treatments may work. Encouraged by these promising results, the Soragni Lab has initiated a clinical trial to further explore the use of PDTOs to predict osteosarcoma therapy responses. Dr. Soragni will describe the study design for this first-of-its-kind, organoid-based clinical trial in sarcoma.Alice Soragni, PhD, is an Associate Professor in the David Geffen School of Medicine at UCLA, and a member of the Jonsson Comprehensive Cancer Center. She has a Bachelor and Master of Science cum Laude from the University of Bologna, Italy, and a PhD from the ETH of Zuerich, Switzerland. Her laboratory couples basic research into mechanisms of disease to the development of novel therapeutic strategies. Her expertise lies in the development of tumor organoid models to investigate the biology of rare tumors such as osteosarcoma and perform screenings for functional precision medicine applications.