RAR and RXR modulation in cancer and metabolic disease.
Retinoic acid receptors (RARs) are ligand-controlled transcription factors that function as heterodimers with retinoid X receptors (RXRs) to regulate cell growth and survival. The success of RAR modulation in the treatment of acute promyelocytic leukaemia (APL) has stimulated considerable interest in the development of RAR and RXR modulators. This has been aided by recent advances in the understanding of the biological role of RARs and RXRs and in the design of selective receptor modulators that might overcome the limitations of current drugs. Here, we discuss the challenges and opportunities for therapeutic strategies based on RXR and RAR modulators, with a focus on cancer and metabolic diseases such as diabetes and obesity.
Altucci
Lucia
L
Dipartimento di Patologia Generale, Seconda Università degli Studi di Napoli, Vico Luigi de Crecchio 7, 80138 Napoli, Italy.
Leibowitz
Mark D
MD
Ogilvie
Kathleen M
KM
de Lera
Angel R
AR
Gronemeyer
Hinrich
H
D002986:Clinical Trials as Topic; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047488:Retinoid X Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D012176:Retinoids / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use
D008024:Ligands; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids