Targeting SUMO2 Protein with Blocker Drugs Shows Promise Against Synovial Sarcoma

Recent research highlights a promising new approach to treat synovial sarcoma, a rare and aggressive cancer affecting soft tissues near large joints. Scientists have identified that the small ubiquitin-like modifier 2 (SUMO2) protein plays a crucial role in the growth and maintenance of synovial sarcoma cells. By using a small molecule called TAK-981 to inhibit SUMO2, researchers observed a significant decrease in tumor cell proliferation and a reduction in the activity of cancer-associated genes, including the oncogenic SS18::SSX fusion protein that characterizes this disease.

This groundbreaking study, published in The EMBO Journal, was conducted by teams from Sanford Burnham Prebys Medical Discovery Institute, UCLA, UC San Diego, and the University of Edinburgh. They harnessed public genomic data from the Dependency Map (DepMap) consortium to identify genes vital for synovial sarcoma cell survival, pinpointing SUMO2 as a key vulnerability. Subsequent experiments demonstrated that inhibiting SUMO2 impairs the growth of cancer cells in both culture and animal models and decreases levels of the oncogenic fusion protein.

Synovial sarcoma typically develops in muscles or ligaments around major joints like the knees, often affecting adolescents and young adults. Although early diagnosis is common, metastasis occurs in nearly 20% of cases, complicating treatment and lowering survival rates to around 50-60% over five years. Given the limited targeted treatment options, these findings could pave the way for new therapeutic strategies.

Dr. Rema Iyer, the study's lead author, explained that targeting SUMO2 could reverse abnormal genetic rewiring caused by the fusion oncoproteins driving the disease. Senior author Dr. Ani Deshpande emphasized that SUMO2 inhibitors like TAK-981 could be especially effective when combined with traditional chemotherapy agents. These results suggest that SUMO2 inhibition might be a viable and potent approach for managing synovial sarcoma and possibly other cancers, such as acute myeloid leukemia and pancreatic cancer. The research opens a new avenue for precision medicine efforts aiming to improve outcomes for patients with this challenging disease.