New Insights into the Molecular Pathway Driving Advanced Prostate Cancer

Researchers at the University of Kentucky Markey Cancer Center have uncovered a critical cellular pathway that propels the progression of aggressive and treatment-resistant prostate cancer. Published in the renowned Journal of Clinical Investigation, the study reveals that the protein RSK1 activates a feedback loop involving TRIM28 and E2F1 proteins, which together promote tumor growth and resistance to hormone therapy. This discovery offers promising avenues for new treatments targeting this pathway, especially for patients whose cancers no longer respond to conventional hormone-based therapies.

The study was led by Dr. Ka Wing Fong, who explained that blocking RSK1 with specific inhibitors halted the feedback loop and significantly reduced tumor growth in laboratory models, including cell cultures and mice. Importantly, these RSK1 inhibitors demonstrated efficacy against tumors deficient in the RB1 gene, which are typically resistant to current therapies like CDK4/6 inhibitors.

Additional findings showed that TRIM28 levels are markedly elevated in patients with advanced prostate cancer, suggesting this pathway becomes more active as the disease progresses. Since RSK inhibitors are already in clinical trials for other cancers, these findings have the potential for rapid translation into new treatment options for castration-resistant prostate cancer (CRPC). This could significantly impact patient outcomes by providing alternative therapies for tumors resistant to standard treatments.

Overall, this research highlights the importance of targeting specific molecular pathways to combat drug-resistant prostate cancer, paving the way for innovative, more effective therapeutic strategies.

Source: https://medicalxpress.com/news/2025-08-molecular-pathway-advanced-prostate-cancer.html