Vitamin D3 and vitamin D3 analogues as an adjunct to cancer chemo-therapy and radiotherapy.
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 D(3)receptor and to be susceptible to growth arrest and/or cell death in response to Vitamin D(3)and its analogues. The hypercalcemia that generally accompanies the utilization of pharmacological concentrations of Vitamin D(3) has been ameliorated in part through the development of Vitamin D(3) analogues. Studies in cell culture and in animal model systems as well as clinical trials have established the potential utility of Vitamin D(3) and Vitamin D(3) analogues as agents which can enhance the antiproliferative and/or cytotoxic effects of conventional chemotherapeutic drugs as well as ionizing radiation. Consequently, Vitamin D(3) and Vitamin D(3) analogues, utilized at concentrations which produce limited hypercalcemia, are likely to prove effective as adjuncts to conventional chemotherapy and radiotherapy.
Gewirtz
David A
DA
Department of Pharmacology, Virginia Commonwealth University/Medical College of Virginia, Richmond, VA 23298, USA. gewirtz@hsc.vcu.edu
Gupta
Mona S
MS
Sundaram
Sujatha
S
D000818:Animals; D017024:Chemotherapy, Adjuvant; D002762:Cholecalciferol / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004357:Drug Synergism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy; D018714:Radiotherapy, Adjuvant
D002762:Cholecalciferol