Researchers at the UCLA Health Jonsson Comprehensive Cancer Center have developed a significant collection of sarcoma patient-derived organoids, which can be used to better understand the disease and identify personalized treatment options. Sarcomas are rare and complex cancers that can develop in the bones or soft tissues, making it challenging to determine the most effective therapies for individual patients. This new approach, detailed in the journal Cell Stem Cell, utilizes patients’ own tumor cells to replicate the unique characteristics of their tumors, enabling researchers to quickly screen a large number of drugs to identify the most suitable treatments.
Dr. Alice Soragni, the senior author of the study, explains that choosing the most effective treatment for sarcoma patients is akin to searching for a needle in a haystack, due to the rarity and diversity of these cancers. Traditional therapies may not be effective for all patients, emphasizing the need for personalized treatment options. The use of patient-derived tumor organoids has the potential to predict how a patient will respond to a specific treatment, ultimately improving outcomes for patients with limited treatment options. Sarcomas account for less than 1% of all cancers but have a high mortality rate, especially among young people, making research in this area crucial.
In an effort to enhance the understanding of sarcomas and predict how a patient’s tumor might respond to various treatments, the research team created a biobank of 294 samples from 126 UCLA patients diagnosed with 25 different subtypes of bone and soft tissue sarcoma. The development of tumor organoids from over 110 samples allowed for high-throughput drug screening using a mini-ring pipeline developed by the team. This method enabled the testing of hundreds of drugs in a 3D format, leading to the identification of potentially effective treatments for a majority of the samples. The responses observed in the lab were shown to match how patients responded to treatment in real-life scenarios, highlighting the potential of organoids in guiding clinical decisions.
Dr. Noah Federman, a study author and director of the UCLA Health Jonsson Comprehensive Cancer Center’s Pediatric Bone and Soft Tissue Sarcoma Program, emphasizes the importance of identifying the most effective drugs for individual patients. The study showed that sarcoma organoids could be generated quickly after surgery or biopsy and used to screen a variety of drugs, including FDA-approved therapies and those in clinical trials. This approach offers a valuable tool for precision medicine in sarcoma patients, where genomic precision medicine has often been insufficient. Additionally, the study demonstrated the feasibility of implementing a large-scale precision medicine program within a single institution, offering a streamlined and scalable testing model.
The team plans to validate their findings in a larger clinical trial focusing on osteosarcoma, the most common type of bone cancer that predominantly affects children and young adults. Dr. Nicholas Bernthal, chair of the Department of Orthopaedic Surgery at UCLA, believes that organoids have the potential to match patients with the most promising therapies, leading to better and more personalized care for sarcoma patients. The study’s first authors include Ahmad Shihabi, Peyton Tebon, and Huyen Thi Lam Nguyen, along with other collaborators from UCLA. The study was supported by grants from the National Cancer Institute, the Alan B. Slifka Foundation, and the David Geffen School of Medicine at UCLA, among others.
Overall, the development of sarcoma patient-derived organoids represents a significant advancement in understanding and treating these complex cancers. By utilizing organoids to test a variety of drugs and predict individual treatment responses, researchers are paving the way for personalized care for sarcoma patients. The success of this approach in identifying effective treatments demonstrates the potential of organoids as a powerful tool in guiding clinical decisions and improving patient outcomes. The team’s ongoing research and plans for a larger clinical trial aim to further validate the effectiveness of this innovative approach in predicting treatment responses in sarcoma patients.
