Retinoids

Retinoids are natural and synthetic derivatives of vitamin A. The anticancer properties of retinoids have been extensively investigated in the preclinical, epidemiological and clinical settings. The primary targets of the retinoids are retinoid receptors. Retinoid receptors are ligand-activated transcription factors, members of the steroid nuclear receptor family. Retinoid receptors are deregulated in a number of malignant diseases including the fusion of RARa with PML in acute promyelocytic leukemia (APL) and the repression of RARß in lung and head and neck cancers. In some cases, pharmacologic doses of retinoids can overcome these cancer specific defects in retinoid signaling. High-doses of retinoids induce differentiation and apoptosis of tumor cells, which is related to their physiologic effects in regulating embryonic development and maturation during hematopoiesis and in diverse epithelial tissues. Retinoid receptors have been cancer therapy targets for more than 30 years, and there are a number of FDA-approved retinoid-based therapies, the most impactful is the standard of care of all-trans-retinoic acid induced differentiation therapy of APL. Clinical evaluation of retinoids, especially newer synthetic retinoids in combination with molecular targeted and epigenetic therapy remains an active area of investigation in oncology.