Retinoids in clinical cancer therapy.

Abstract

Retinoids constitute a class of naturally occurring and synthetic compounds that are structurally related to vitamin A. The chemical structure of retinoids consists of a cyclic end group (trimethylcyclohexenyl ring) and a dimethyl substituted tetraene chain, ending in a polar hydroxyl, aldehyde, or carboxyl group. Naturally occurring retinoids include vitamin A (all-trans retinol) and its oxidative metabolites: retinaldehyde, all-trans-retinoic acid (tRA), and 13-cis-retinoic acid (13-cRA). Four additional naturally occurring retinoids have been newly discovered in the past 5 years: 9-cis-retinoic acid (9-cRA) [1,2], 3,4-didehydroretinoic acid [3], 14-hydroxy retro-retinol [4], and more recently, 9-cis, 13-cis-retinoic acid [5,6]. The potential for the existence of 11-cis and 15-cis-retinoic acid is very high [7]. Retinoic acid isomers are generated by changes in the position and chemical nature of the double bonds in the tetraene chain (Figure 1). The clinical use of retinoids in oncology has been dominated by tRA, 13-cRA, and more recently 9-cRA, which are the focus of this discussion. Esters of all-trans retinol (vitamin A), particularly retinol palmitate, have also been used as cancer chemopreventive or chemotherapeutic agents [8–10] but will not be discussed in this presentation.KeywordsRetinoic AcidAcute Promyelocytic LeukemiaRetinoic Acid ReceptorPromyelocytic Leukemia Zinc FingerSynthetic RetinoidThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.