Naturally occurring and synthetic
vitamin A metabolites and analogs (
retinoids) inhibit
tumor development in a variety of cellular, animal, and patient studies. They suppress transformation of cells in vitro and inhibit
carcinogenesis in various organs in animal models. In a mouse skin
carcinogenesis model, topical
retinoids exhibit suppressive effects on
tumor promotion, but have no effect on
tumor initiation. In other models,
retinoids administered in the diet suppress
tumor development even in an adjuvant setting after excision of the first
tumor.
Retinoids suppress
carcinogenesis in individuals with premalignant lesions and a high risk to develop
cancer of the aerodigestive tract. Likewise,
retinoids prevent the development of
second primary cancers in head/neck and
lung cancer patients who had been treated for the first primary. The mechanisms underlying the anticarcinogenic activity of
retinoids appear to be associated with the ability of
retinoids to modulate the growth, differentiation, and apoptosis of normal, premalignant, and malignant cells in vitro and in vivo. Most of these effects are mediated by nuclear
retinoid receptors, but other mechanisms may also be involved. These studies indicate that
retinoids are potentially useful agent for
cancer chemoprevention.