INTRODUCTION AND MECHANISMS OF ACTION

Vitamin A, its physiologic metabolites, and synthetic derivatives (retinoids) have been shown to have protective effects against the development of certain types of cancer. Oral retinoids can be used to reduce and delay the development of skin cancer in organ transplant recipients. Patients who may benefit most from retinoid chemoprevention are those who are actively developing large numbers of skin cancers or individual high-risk skin cancers.

Retinoids are a class of natural or synthetic compounds related to vitamin A that display a wide range of biological activity. Retinoids play an important role in the inhibition of cell growth, epithelial cell differentiation, and the induction of cell death and have antiproliferative and cancerprotective properties. Retinoids have also immunomodulating effects.

It is largely unknown how retinoids act beneficially in the prevention of skin cancer. The chemoprevention effect of retinoids is most likely exerted at the tumor-promotion phase of carcinogenesis. Known effects of retinoids include reduction of proliferation and keratinization, induction of apoptosis, and immunomodulation.

In a study with 33 renal-transplant recipients, biopsies were taken before and after 3 months of treatment with acitretin in doses up to 0.4 mg/kg/day. Histological and immunohistochemical parameters for dysplasia, epidermal thickness, proliferation, differentiation, apoptosis, and dermal inflammation were analyzed. Following acitretin treatment, a significant reduction in epidermal thickness and increase in normal differentiation parameter K10 was observed. Epidermal proliferation did not change, nor did apoptosis and inflammation.