Retinoid Signaling in Cancer and Its Promise for Therapy

Abstract

Deregulated signal transduction is a major facet of cancer development and progression. Herein, we review the current paradigm for retinoic acid signaling, its role in cancer and potential therapeutic applications and challenges. Retinoic acid is used with remarkable success in the treatment of one of the most high-risk leukemias, acute promyelocytic leukemia; however, extending its use in the treatment of other cancers has had limited success at best. Functional studies provide clues for the poor performance of retinoic acid as a general cancer therapeutic, connecting retinoic acid signaling to both cell growth arrest and proliferation with tumor suppression and cancer progression consequences. The dualistic role of the retinoic acid signaling pathway in cancer is revealed in its gene transcription targets, cross-talk with other transcription factors, mediation of apoptotic pathways, and influence in the immune system. If the greatest potential benefit of retinoid-based cancer therapeutics is to be achieved, the many physiological roles of retinoic acid need to be considered.