Researchers at the UCLA Health Jonsson Comprehensive Cancer Center have created the largest collection of personalized organoid models for sarcoma patients, offering a potential pathway to data-driven, individualized treatment decisions. The platform aims to address the limited treatment options and poor outcomes associated with this rare and heterogeneous cancer.
Addressing a Critical Unmet Need in Sarcoma
Sarcomas, comprising over 100 distinct tumor types arising from bone, connective, and soft tissues, present a significant challenge due to the lack of patient-derived models for studying disease biology and personalizing treatment. Dr. Alice Soragni, the study's senior author and assistant professor at UCLA, emphasized the opportunity to leverage the expertise of UCLA's Sarcoma program to develop these models and advance precision medicine.
Creating and Characterizing Sarcoma Organoids
The research team collected 194 tumor samples from 126 UCLA patients, representing 24 different sarcoma subtypes. They successfully generated patient-derived tumor organoids from 114 samples, encompassing 21 sarcoma diagnoses. Detailed histopathological and molecular analyses confirmed that these organoids retained key characteristics of the original tumors, validating their utility as representative models.
High-Throughput Drug Screening for Personalized Treatment
The organoids were subjected to high-throughput drug screening using a mini-ring pipeline developed by Dr. Soragni's team. An average of 117 drugs were tested per sample, with the screening panel tailored to individual characteristics, histology, patient-specific data, and clinical background. The selection criteria focused on FDA-approved therapies and NCCN-recommended combination regimens, as well as drugs targeting genetic alterations identified in the samples.
Promising Results and Clinical Implications
The drug screenings yielded results within a week, identifying at least one potentially effective FDA-approved or NCCN-recommended regimen for 59% of the specimens. Dr. Soragni cautioned that while these drugs are approved for cancer, only a small portion is specifically approved for the cancer type they were effective against in the screening. However, she suggested that validation in clinical trials could broaden drug use, particularly for rare or difficult-to-treat cancers.
Notably, the drug responses observed in the organoids matched how the patients responded to treatment in a small number of cases, suggesting the potential of organoids to guide clinical decisions. The team has initiated PREMOST, a clinical trial to evaluate the feasibility of the organoid platform in predicting responses to neoadjuvant therapy in osteosarcoma patients and to investigate second-line therapies for recurrent and metastatic osteosarcoma.
Future Directions and Scalability
Dr. Soragni believes that organoids should be generated for all patients, ideally as early as possible, to provide a more representative picture of tumor evolution and heterogeneity. The optimized tissue handling and freezing protocols developed in this study will facilitate the receipt of high-quality tissue from external partners, enabling large-scale implementation of organoid-based programs across institutions.
