All-trans-retinoic acid and cutaneous cancers.

All-trans-retinoic acid (tretinoin) is a biologically active metabolite of vitamin A. Topical tretinoin has been shown to have antineoplastic activity in a variety of experimentally induced and naturally occurring tumors. In some animal studies it has inhibited the development of ultraviolet-induced carcinomas. However, in other studies it accelerated such ultraviolet tumorigenesis. Other work has shown that the drug can eradicate chemically induced papillomas and carcinomas. These various effects may stem from tretinoin's influences on deoxyribonucleic acid synthesis, polyamine enzyme systems, sister-chromatid exchanges, oncogene expression, or lysosome lability. In clinical trials, tretinoin removed premalignant actinic keratoses from the face. Combined with 5-fluorouracil, it is also quite effective in the treatment of such lesions on the forearms and hands, areas where neither agent alone has much effect. It should be emphasized that tretinoin has not been shown to be carcinogenic in either animals or humans. After more than a decade of topical use of tretinoin on human skin, there is no evidence that the drug either initiates or promotes carcinogenesis in humans.