Alkylating Derivatives of Vitamin D Hormone for Prostate Cancer

摘要

Prostate cancer (PCa) is the most prevalent cancer among men, and second leading cause of cancer death among men in the US. Current clinical interventions for PCa include surgery and radiation therapy, and anti-hormone and androgen-deprivation therapy for early stage and hormone-sensitive PCa. But, practically no therapy is currently available for non-resectable and hormone- refractory PCa. We have developed 1alpha,25-Dihydroxyvitamin D3-3-bromoacetate (1,25(OH)2D3-3-BE), a novel alkylating derivative of 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3), and in preliminary studies, demonstrated potent growth- inhibitory activity in several PCa cells. These results suggest a strong therapeutic potential of this compound in PCa. The principal goal of this project is to evaluate the potential of 1,25(OH)2D3-3-BE as a therapeutic agent for prostate cancer in animal models of human prostate cancer, and explore the molecular mechanism/s of this compound in prostate cancer cells. The ultimate goal of this project is to develop 1,25(OH)2D3-3-BE as a therapeutic agent for prostate cancer.