An Organoid Revolution in Sarcoma Treatment – Rapid, Personalized Drug Testing

Personalized approaches to cancer treatment are revolutionary in developing strategies suited to each patient's genetics and tumor characteristics. Finding effective treatments can be particularly challenging in rare, complex tumors with many subtypes, such as sarcomas. New research suggests that using sarcoma organoids for drug screening may offer promising results for personalized treatment. The study identified active, approved or recommended treatment options for 58% of patients screened using organoids.

What Are Sarcoma Organoids and Why Do They Matter?

Organoids are laboratory-grown models derived from a patient's tumor samples, consisting of three-dimensional cell structures. They can closely reflect a tumor's biological behavior and play an important role in understanding intratumoral heterogeneity. Based on an individual's tumor characteristics, they allow different drugs to be tested simultaneously and the most effective treatment strategies to be identified.

A Notable Organoid Study

A study in Cell Stem Cell , published on September 20, 2024,by UCLA's Dr. Alice Soragni and colleagues showed that sarcoma organoids could enable rapid drug screening and personalized treatment selection. After biopsy or surgery, organoids were generated within one week and many drugs were tested.

Study Details: 194 Tumor Samples and 24 Sarcoma Subtypes

The research examined 194 tumor samples from 126 patients treated for sarcoma at UCLA between February 2018 and May 2022. They represented 24 sarcoma subtypes, including osteosarcoma, chordoma, chondrosarcoma, leiomyosarcoma and undifferentiated pleomorphic sarcoma. Organoids were generated from suitable samples, and chemotherapy and targeted agents were tested both alone and in combinations.

At least 10 drugs were screened in 92 samples, and at least one significant drug response was observed in 80.4%. For example, a synovial sarcoma was sensitive to trametinib, while a CIC-rearranged sarcoma was sensitive to gemcitabine plus docetaxel.

Interesting Findings: Osteosarcoma and Drug Sensitivity

The findings also revealed differences in drug sensitivity between sarcoma subtypes. For example, osteosarcoma organoids were more sensitive than the average across sarcoma types to ceralasertib (P =0.00026), topotecan (P =0.028), cabozantinib (P =0.024) and everolimus (P =0.012). This suggests that osteosarcoma responds better to these drugs than other sarcomas.

Clinical characteristics, including age, disease stage and number of prior treatments, also influenced drug sensitivity. For example, organoids from older patients were more resistant to cediranib than those from pediatric or young adult patients.

FDA-Approved Drugs and New Treatment Paths

The researchers identified the five most effective treatments for each sample, creating 203 drug–diagnosis matches. These included the FDA approval status of drugs found active against particular sarcoma subtypes. The study found that 4% were FDA-approved for the same sarcoma type, while 31% were approved for other cancers . A further 1% were being evaluated in clinical trials for the sarcoma type identified, and 21% were in trials for other cancers. However, 43% had not yet entered clinical trials or had been discontinued from development.

New Horizons in Personalized Treatment: Clinical Trials and the Future

An important finding was the identification of active, approved or recommended treatment options for 58% of patients screened using sarcoma organoids. This rapid, effective process may offer oncologists actionable strategies within just one week after biopsy or surgery.

The researchers aim to predict responses to MAP (methotrexate, doxorubicin and cisplatin) in osteosarcoma patients through a clinical trial they have launched. It investigates responses to FDA-approved drugs in osteosarcoma patients.

Conclusion

This drug-screening study using sarcoma organoids again highlights the importance of personalized cancer treatment. Rapid generation of organoids after biopsy or surgery plays an important role in assessing current options and identifying new strategies. The study represents a promising step toward personalized treatment for difficult-to-treat tumors such as sarcomas.