PMID- 26970124 OWN - NLM STAT- MEDLINE DCOM- 20160719 LR - 20220321 IS - 1532-8708 (Electronic) IS - 0093-7754 (Print) IS - 0093-7754 (Linking) VI - 43 IP - 1 DP - 2016 Feb TI - Retinoids and rexinoids in cancer prevention: from laboratory to clinic. PG - 49-64 LID - S0093-7754(15)00167-0 [pii] LID - 10.1053/j.seminoncol.2015.09.002 [doi] AB - Early in the age of modern medicine the consequences of vitamin A deficiency drew attention to the fundamental link between retinoid-dependent homeostatic regulation and malignant hyperproliferative diseases. The term "retinoid" includes a handful of endogenous and a large group of synthetic derivatives of vitamin A. These multifunctional lipid-soluble compounds directly regulate target genes of specific biological functions and critical signaling pathways to orchestrate complex functions from vision to development, metabolism, and inflammation. Many of the retinoid activities on the cellular level have been well characterized and translated to the regulation of processes like differentiation and cell death, which play critical roles in the outcome of malignant transformation of tissues. In fact, retinoid-based differentiation therapy of acute promyelocytic leukemia was one of the first successful examples of molecularly targeted treatment strategies. The selectivity, high receptor binding affinity and the ability of retinoids to directly modulate gene expression programs present a distinct pharmacological opportunity for cancer treatment and prevention. However, to fully exploit their potential, the adverse effects of retinoids must be averted. In this review we provide an overview of the biology of retinoid (activated by nuclear retinoic acid receptors [RARs]) and rexinoid (engaged by nuclear retinoid X receptors [RXRs]) action concluded from a long line of preclinical studies, in relation to normal and transformed states of cells. We will also discuss the past and current uses of retinoids in the treatment of malignancies, the potential of rexinoids in the cancer prevention setting, both as single agents and in combinations. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Uray, Ivan P AU - Uray IP AD - Department of Clinical Cancer Prevention, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA. Electronic address: ivanpeteruray@gmail.com. FAU - Dmitrovsky, Ethan AU - Dmitrovsky E AD - Department of Clinical Cancer Prevention, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA. FAU - Brown, Powel H AU - Brown PH AD - Department of Clinical Cancer Prevention, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA. LA - eng GR - P30CA16672/CA/NCI NIH HHS/United States GR - R03CA180550/CA/NCI NIH HHS/United States GR - P30 CA016672/CA/NCI NIH HHS/United States GR - R01-CA087546/CA/NCI NIH HHS/United States GR - R01 CA111422/CA/NCI NIH HHS/United States GR - R03 CA180550/CA/NCI NIH HHS/United States GR - R01 CA062275/CA/NCI NIH HHS/United States GR - R01 CA087546/CA/NCI NIH HHS/United States GR - R01-078480/PHS HHS/United States GR - R01-CA062275/CA/NCI NIH HHS/United States GR - R01 CA078480/CA/NCI NIH HHS/United States GR - R01-CA190722/CA/NCI NIH HHS/United States GR - R01 CA190722/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20150925 PL - United States TA - Semin Oncol JT - Seminars in oncology JID - 0420432 RN - 0 (Anticarcinogenic Agents) RN - 0 (Receptors, Retinoic Acid) RN - 0 (Retinoid X Receptors) RN - 0 (Retinoids) SB - IM MH - Animals MH - Anticarcinogenic Agents/metabolism/therapeutic use MH - Chemoprevention MH - Humans MH - Neoplasms/drug therapy/*prevention & control MH - Nervous System Diseases/drug therapy MH - Pulmonary Disease, Chronic Obstructive/drug therapy MH - Receptors, Retinoic Acid/*metabolism MH - Retinoid X Receptors/*metabolism MH - Retinoids/adverse effects/*metabolism/*therapeutic use MH - *Signal Transduction MH - Skin Diseases/drug therapy PMC - PMC4789177 MID - NIHMS725738 OTO - NOTNLM OT - Cancer prevention OT - Combination OT - Medical use OT - Retinoid OT - Rexinoid COIS- COI statement: Dr. Uray has no conflicts of interest. COI statement: Dr. Dmitrovsky has no conflicts of interest. COI statement: Dr. Brown is on the Scientific Advisory Board of Susan G. Komen for the Cure. EDAT- 2016/03/13 06:00 MHDA- 2016/07/20 06:00 PMCR- 2017/02/01 CRDT- 2016/03/13 06:00 PHST- 2016/03/13 06:00 [entrez] PHST- 2016/03/13 06:00 [pubmed] PHST- 2016/07/20 06:00 [medline] PHST- 2017/02/01 00:00 [pmc-release] AID - S0093-7754(15)00167-0 [pii] AID - 10.1053/j.seminoncol.2015.09.002 [doi] PST - ppublish SO - Semin Oncol. 2016 Feb;43(1):49-64. doi: 10.1053/j.seminoncol.2015.09.002. Epub 2015 Sep 25.