Investigators have created the largest known collection of organoids derived from sarcoma patients, which can enhance the understanding of this disease and help pinpoint the most effective therapies for each individual. By utilizing 3D mini tumor models that closely mimic a patient’s tumor, treatment strategies can be better customized, marking progress towards personalized cancer care.
At the UCLA Health Jonsson Comprehensive Cancer Center, researchers have established the largest collection of patient-derived organoids for sarcoma, designed to improve the understanding of this disease and to help identify the therapies that are most suitable for each patient.
This innovative method, published in the journal Cell Stem Cell, employs tumor cells from patients that replicate the unique properties of their tumors. This enables scientists to efficiently assess a wide range of drugs to find tailored treatments for this rare and varied category of cancers.
“Sarcoma is a rare and intricate disease, complicating the process of conducting clinical trials to discover effective therapies. Some less common subtypes have no standard treatment options. Additionally, even when multiple therapies exist, there is often no reliable data-based approach to determine the most effective treatment for a specific patient. Finding the right treatment can feel like looking for a needle in a haystack,” explained Dr. Alice Soragni, the lead author and an assistant professor in the Department of Orthopaedic Surgery at the David Geffen School of Medicine at UCLA. “Using organoids derived from patient tumors allows us to better predict how a patient may respond to treatment, ultimately aiming to enhance outcomes for individuals facing these often-limited treatment options.”
Although sarcomas occur in the bones or soft tissues like muscles and fat, they represent less than 1% of all cancer cases but have a significantly high mortality rate, especially among younger populations. The diversity of sarcoma types, exceeding 100 distinct subtypes, makes research particularly challenging. Responses to standard therapies can vary widely, complicating the selection of the most effective treatment for each patient.
To investigate whether organoids could improve understanding of tumor responses to specific medications or combinations, the research team built a biobank comprising 294 samples from 126 UCLA patients diagnosed with 25 different subtypes of bone and soft tissue sarcoma. While tumor organoids are commonly used to explore carcinomas, this study is the first at such a scale to extend this technique to sarcoma.
The researchers successfully generated tumor organoids from over 110 samples and performed thorough histopathological and molecular analyses to confirm that these organoids retained the essential characteristics of the original tumors. Subsequently, they subjected the organoids to high-throughput drug screening using a rapid testing pipeline designed by Soragni and her team, which allowed for the assessment of numerous drugs in a 3D format efficiently.
This approach led to the identification of at least one potentially effective treatment approved by the U.S. Food and Drug Administration (FDA) for 59% of the samples tested. Moreover, in a few instances, the drug reactions observed in the lab corresponded with how the patients themselves responded to the treatments, indicating that these organoids could serve as a valuable tool in guiding clinical choices.
“We have proven that sarcoma organoids can be quickly generated—typically within a week post-surgery or biopsy—and that we can use them to test a large number of medications, including FDA-approved drugs and those currently in clinical trials,” stated Soragni.
“This capability enables us to determine which drugs are most likely to be effective for individual patients, which is vital for the intricate nature of sarcoma, where genomic precision medicine has frequently faced challenges,” added Dr. Noah Federman, one of the study’s authors, as well as the Glaser Family Endowed Chair and director of the Pediatric Bone and Soft Tissue Sarcoma Program at the UCLA Health Jonsson Comprehensive Cancer Center.
The findings from this study also illustrate that a sizable, functional precision medicine program can feasibly operate within a single institution, providing a streamlined and scalable approach to organoid-based testing.
“Organoids create a tangible method for aligning patients with the most promising therapies, potentially revolutionizing care for sarcoma patients,” remarked Dr. Nicholas Bernthal, chair and executive medical director of the Department of Orthopaedic Surgery at UCLA. “We are hopeful that this strategy will lead to improved, more personalized care for those in need.”
In light of this study’s outcomes, the UCLA team plans to validate their findings through a larger clinical trial aimed at confirming the effectiveness of the organoid-based method in predicting treatment responses in patients with osteosarcoma, which is the most common type of bone cancer primarily affecting children and young adults.
Soragni, Federman, and Bernthal are all affiliated with the UCLA Health Jonsson Comprehensive Cancer Center. The study’s leading authors include Ahmad Shihabi, a project scientist in Soragni’s lab; Peyton Tebon, a visiting project scientist; and Huyen Thi Lam Nguyen, a graduate student. Additional authors from UCLA include Sara Sartini, Ardalan Davarifar, Alexandra Jensen, Miranda Diaz-Infante, Hannah Cox, Alfredo Enrique Gonzalez, Summer Swearingen, Helena Winata, Sorel Fitz-Gibbon, Takafumi Yamaguchi, Jae Jeong, Sarah Dry, Arun Singh, Bartosz Chmielowski, Joseph Crompton, Fritz Eilber, Scott Nelson, Paul Boutros, and Jane Yanagawa.
The study received funding from the National Cancer Institute, the Alan B. Slifka Foundation, the David Geffen School of Medicine at UCLA, and the UCLA Health Jonsson Comprehensive Cancer Center.
