Inhibition of chemical carcinogenesis by retinoids.

Retinoids are effective inhibitors of chemical carcinogenesis in the mammary gland, esophagus, and urinary bladder of experimental animals. Modification of the basic retinoid structure has produced retinoids with increased target organ specificity, resulting in increased anticancer activity with reduced systemic toxicity. Combining retinoid treatment with hormonal manipulation results in a synergistic inhibition of mammary carcinogenesis; this combination approach also inhibits mammary tumor recurrence following surgical removal of the first mammary tumor. Retinoids are most effective when administered shortly after the carcinogenic insult. However, even when retinoid treatment if delayed, the compounds are still effective cancer chemopreventive agents for the mammary gland and urinary bladder. The length of time that retinoid exposure can be delayed and retain an anticancer effect is directly related to tumor latency, with a longer delay permissible against tumors with long latent periods. Current research focuses on the identification of new retinoids with increased chemopreventive activity and decreased toxicity, and combination studies which will provide treatment regimens with increased anticancer activity as well as information pertaining to mechanisms of retinoid action.