Affiliation: Department of Medicine Virginia Commonwealth University Medical College of Virginia P.O. Box 980230 Richmond.
The development of drugs that are highly selective and yet produce minimal toxicity to host tissue remains one of the most difficult challenges in cancer therapeutics. Since the majority of malignancies are treated with drugs in combination rather than single agents, one practical approach to circumvent this problem is to develop new therapeutic agents that will potentiate the effectiveness of current clinical protocols. This strategy would accelerate the acceptance of new drugs as adjunct therapies since these agents could be used at concentrations well below their maximal tolerated doses. Tumor cells derived from a variety of different sources have been shown to express the Vitamin D3 receptor and to be susceptible to growth arrest and/or cell death in response to Vitamin D3 and its analogues. The hypercalcemia that generally accompanies the utilization of pharmacological concentrations of Vitamin D3 has been ameliorated in part through the development of Vitamin D3 analogues. Studies in cell culture and in animal model systems as well as clinical trials have established the potential utility of Vitamin D3 and Vitamin D3 analogues as agents which can enhance the antiproliferative and/or cytotoxic effects of conventional chemotherapeutic drugs as well as ionizing radiation. Consequently, Vitamin D3 and Vitamin D3 analogues, utilized at concentrations which produce limited hypercalcemia, are likely to prove effective as adjuncts to conventional chemotherapy and radiotherapy.