Retinoid Targets for the Treatment of Cancer

Abstract

Retinoic acid (RA), the most potent natural retinoid, is essential for normal cell growth and differentiation. The RA signaling pathway is multistep, involving the precise regulation of retinoid levels and the control of RA-dependent gene expression in target cells. Within this complex scheme, there are many different aberrations in the RA signaling pathway of tumor cells that have been found to be associated with abnormal cell growth and tumorigenesis. This article reviews the normal pathways of RA signaling, followed by a discussion of the various sites that have been implicated in tumorigenesis and targeted for drug development. Currently, there are several retinoids and one rexinoid approved for the treatment of specific cancers. Future experimentation in drug discovery will continue to explore the efficacy of retinoids/rexinoids, either alone or in combination with other chemotherapeutic agents and/or chromatin remodeling agents, and the development of agents to modulate RA metabolism within cells. It is likely that different drug treatments will be developed that are specifically tailored to the unique point(s) in the RA signaling pathways that are aberrant in specific types of tumor cells.