Vitamin A is essential for normal cellular growth and differentiation. A vast amount of laboratory data have clearly demonstrated the potent antiproliferative and differentiation-inducing effects of
vitamin A and the synthetic analogues (
retinoids). Recent in-vitro work has led to the exciting proposal that
protein kinase-C may be centrally involved in many of
retinoids' anticancer actions including the effects on
ornithine decarboxylase induction, intracellular
polyamine levels, and
epidermal growth factor receptor number. Several intervention trials have clearly indicated that natural
vitamin A at clinically tolerable doses has only limited activity against human
neoplastic processes. Therefore, clinical work has focused on the synthetic derivatives with higher therapeutic indexes. In human
cancer prevention,
retinoids have been most effective for
skin diseases, including
actinic keratosis,
keratoacanthoma,
epidermodysplasia verruciformis,
dysplastic nevus syndrome, and
basal cell carcinoma. Several noncutaneous premaligancies, however, are currently receiving more attention in
retinoid trials. Definite
retinoid activity has been documented in
oral leukoplakia,
laryngeal papillomatosis, superficial bladder
carcinoma,
cervical dysplasia, bronchial
metaplasia, and
preleukemia. Significant therapeutic advances are also occurring with this class of drugs in some
drug-resistant
malignancies and several others that have become refractory, including advanced
basal cell cancer,
mycosis fungoides,
melanoma,
acute promyelocytic leukemia, and
squamous cell carcinoma of the skin and of the head and neck. This report comprehensively presents the clinical data using
retinoids as
anticancer agents in human premalignant disorders and outlines the ongoing and planned studies with
retinoids in combination and adjuvant
therapy.