It is now well established that 1alpha, 25-dihydroxyvitamin D3 not only mediates calcium homeostasis but also has significant cellular activity in tissues not related to calcium homeostasis. This seco-steroid hormone has been shown to promote cellular differentiation and inhibit proliferation in a number of normal and malignant cell lines. As a therapeutic agent for malignancy, 1,25(OH)2D3 has limited potential due to its calcemic activity. We propose to synthesize and evaluate a series of 19-nor-vitamin D analogs and their pro-drug precursors as potential anti-cancer therapeutics. Preliminary studies suggest that these 19-nor compounds retain differentiating and antiproliferative activity and exhibit reduced calcemic activity.
Breast cancer and cancer of the prostate are two of the most common human malignancies with approximately 300,000 new cases being diagnosed each year. Drug therapy for these diseases exceeds 800 million dollars annually. New effective therapeutic agents for treating breast and prostate cancer would have significant human and commercial value.
