Boston University School of Medicine, USA
Rahul Ray is a Professor of Medicine at Boston University School of Medicine. He is an authority in the structure-function and cancer therapeutic areas of the vitamin D endocrine system. He has received numerous extra-mural grants and contracts for his research and four awarded patents. He has served as a member in several National Institutes of Health Study Sections and he is an editorial board member of steroid hormone-related journals.
Non-classical properties of 1α, 25-dihydroxyvitamin D3 (1, 25(OH)2D3), the vitamin D hormone includes inhibition of proliferation and diff erentiation of malignant cells raising its potential as a cancer therapeutic agent. But, therapeutic use of 1, 25(OH)2D3 in various cancers has been limited by the risk of toxicity related to hypercalcemia and hypercalciuria at clinically useful doses, thereby setting the ground for developing 1, 25(OH)2D3-analogs with low toxicity and potent anti-proliferative activity. Our laboratory has developed AMPI-109, a novel alkylating analog of 1, 25(OH)2D3. We observed that AMPI-109 is a signifi cantly stronger anti-proliferative agent than 1, 25(OH)2D3 in several prostate and renal cancer cells. But, AMPI-109 did not inhibit the growth of normal prostate and renal cells. We noted that AMPI-109 is a signifi cantly superior inhibitor of renal cancer cell growth than afi nitor, axitinib, sorafenib and sunitinib, the currently approved drugs for renal cell carcinoma. Most signifi cantly, AMPI-109 strongly inhibited tumor-growth in mouse models of human androgen-insensitive prostate and renal cancers, demonstrating the potential of AMPI-109 as a therapeutic agent in these malignancies. AMPI-109 was initially developed as an affi nity alkylating agent for nuclear vitamin D receptor, the transcriptional factor responsible for the cellular actions of 1,25(OH)2D3. But, our recent studies demonstrate that the anti-proliferative action of AMPI-109 is independent of VDR in prostate and kidney cancer cells, setting AMPI-109 apart from all known analogs of 1,25(OH)2D3. In this presentation we will delineate these results and discuss the potential of AMPI-109 as an eff ective and safe therapeutic agent for androgen-insensitive prostate and renal cancers.