ANTITUMORAL EFFECT OF RETINOIDS: A COMPARISON BETWEEN ALL TRANS RETINOIC ACID AND IIF, A SPECIFIC LIGAND OF RXR

Several studies suggest the employment of retinoids in the therapy of cancer. These molecules, that are natural derivatives of vitamin A or retinol and include the all-trans-retinoic acid (RA), play important roles in modulating normal or tumor cell growth through the regulation of differentiation and/or apoptosis. The clinical use of retinoids is complicated by the fact that the doses needed for successful treatment are often toxic, leading to hypervitaminosis A syndrome; another major problem is that in some patients cancer cells become resistant to these compounds. The retinoid signal is mediated in target cells through specific nuclear receptors: the retinoic acid receptor (RAR) and the retinoid X receptor (RXR). RARs and RXRs are divergent in their ligand specificity; RA can bind and activate only RAR receptors, by contrast, 9-cis- retinoic acid binds RARs and RXRs, but with different affinities. It has been demonstrated that the retinoids that are ligands of RXR are ef