In a groundbreaking study published in the Journal of Clinical Investigation, researchers at The Institute of Cancer Research, London, have discovered that the BCL2 protein is prevalent in a subtype of advanced prostate cancer resistant to hormone therapy. This discovery not only provides a new target for treatment but also a method to predict which patients may become resistant to hormone therapy.
Approximately 10% of prostate cancer patients exhibit high levels of BCL2, a protein that prevents cell death. The research team has initiated a clinical trial testing the BCL2 inhibitor venetoclax, already approved for certain types of leukemia, in combination with the hormone therapy enzalutamide.
Patients with elevated BCL2 levels have shown significantly shorter overall survival rates, with a median of 20.4 months compared to 53.0 months for those with lower levels. Additionally, these patients respond less favorably to common hormone therapies, with only 12.5% experiencing a significant reduction in PSA levels, compared to 47.6% in patients with lower BCL2 expression.
However, the study found no difference in survival or PSA response when patients were treated with the chemotherapy docetaxel, suggesting it may be a more effective treatment option for those with high BCL2 levels. Laboratory experiments targeting the BCL2 'family' of proteins (BCL2, BCLXL, and MCL1) showed promising anti-tumor responses, indicating that a combination therapy approach could be more effective than targeting BCL2 alone.
Dr. Adam Sharp and Professor Johann de Bono emphasized the importance of developing new treatments to improve the quality and quantity of life for patients with advanced prostate cancer. They highlighted the potential for personalized treatment plans based on BCL2 levels and the need for further research into combination therapies and drug delivery technologies that specifically target cancer cells while sparing healthy tissue.
This research represents a significant step forward in understanding and treating aggressive forms of prostate cancer, offering hope for more effective, personalized treatment strategies in the future.
