The development of retinoids in experimental and clinical oncology and dermatology

The retinoids are a class of compounds consisting of vitamin A and its natural and synthetic analogues. Vitamin A has a marked influence on the differentiation of epithelial tissues, such as skin and mucous membranes. Vitamin A deficiency leads to hyperkeratosis of the skin and squamous metaplasia of mucous membranes, histologic features common to various dermatologic and precancerous diseases. The beneficial effect of vitamin A in these diseases was, however, unsatisfactory. Therefore, a retinoid program was set up in order to find new synthetic retinoids with the highest possible therapeutic activity and the least possible side effects. It was discovered that the chemically induced skin papilloma of the mouse responded to retinoids with a marked regression. This therapeutic activity in combination with the determination of a therapeutic index (relation between therapeutic action and hypervitaminosis A syndrome) served as criteria in choosing retinoids for clinical trials in dermatologic and oncologic diseases. Until now three particular compounds have achieved remarkable usefulness in dermatology: 13-cis-retinoic acid (isotretinoin; Accutane) in the treatment of cystic acne, the aromatic retinoid etretinate in the therapy of severe forms of psoriasis, and an arotinoid. Much less spectacular success has been achieved with these compounds in the prevention and therapy of premalignant and malignant diseases. It is hoped that newer retinoids with a still better therapeutic index or a more selective therapeutic activity will further enrich our therapeutic armamentarium in the fields of dermatology, oncology, and other disciplines of medicine.