title: Retinoids and rexinoids in cancer prevention: from laboratory to clinic.
abstract: 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.
authors.affiliation: Department of Clinical Cancer Prevention, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA. Electronic address: ivanpeteruray@gmail.com.
authors.forename: Iván P
authors.initials: IP
authors.lastname: Uray
authors.affiliation: Department of Clinical Cancer Prevention, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Ethan
authors.initials: E
authors.lastname: Dmitrovsky
authors.affiliation: Department of Clinical Cancer Prevention, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Powel H
authors.initials: PH
authors.lastname: Brown
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000378:metabolism / Q000627:therapeutic use; D018890:Chemoprevention; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000517:prevention & control*; D009422:Nervous System Diseases / Q000188:drug therapy; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy; D018168:Receptors, Retinoic Acid / Q000378:metabolism*; D047488:Retinoid X Receptors / Q000378:metabolism*; D012176:Retinoids / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use*; D015398:Signal Transduction; D012871:Skin Diseases / Q000188:drug therapy
chemical_list: D016588:Anticarcinogenic Agents; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids
keywords: Cancer prevention; Combination; Medical use; Retinoid; Rexinoid