There is no curative treatment for prostate cancer patients who develop recurrences after radiation therapy or radical prostatectomy, or patients who have confirmed metastatic disease at the time of diagnosis. Androgen ablation is generally accepted as the best method for treating metastatic prostate cancer. Unfortunately, most patients eventually progress to hormone-refractory prostate cancer, and hormone ablation therapy itself can be associated with disease complications. Given the profound medical impact of prostate cancer and mandate for improved therapies, there is urgent need to develop novel treatments that are efficacious, with minimal toxicity, against systemic diseases.

It would be ideal if a durable antitumor immune response could be provoked during the initial molecular-targeted therapy. This would take advantage of the body's own immune system to effectively eliminate prostate cancer cells, even those disseminated systemically, providing a long-lasting memory effect with low-level or potentially no toxicity. In our proposed study, we intend to develop and evaluate a novel gene-based therapeutic approach, which is capable of efficiently reducing tumor burden and simultaneously mounting an antitumor immune response. In this treatment regimen, an ancient and highly conserved signaling pathway commonly used for the detection of virus is exploited for selectively driving prostate tumor cell death, while a non-toxic physiological immune modulator is engineered to further boost immune responses for attacking tumor cells and providing a long-term protection from tumor recurrence. Using various clinically relevant prostate tumor models, we will assess the therapeutic efficacy of this dual molecular-targeted strategy, which in principle will prove synergistic in both local and systemic control of primary prostate tumors and metastases. Successful testing of this novel therapeutic strategy may provide a unique opportunity to potentially cure advanced prostate cancer patients of their disease. The insights gained from the mechanistic studies we propose will facilitate rational design of improved treatment modalities for advanced prostate cancer. Successful pre-clinical results from this project may lead to rapid translation of this novel approach into the clinic for treatment of human prostate cancer.