Peroxisome proliferator-activated receptor gamma pathway targeting in carcinogenesis: implications for chemoprevention.
The peroxisome proliferator-activated receptor (PPAR) gamma is one member of the nuclear receptor superfamily that contains in excess of 80 described receptors. PPARgamma activators are a diverse group of agents that range from endogenous fatty acids or derivatives (linolenic, linoleic, and 15-deoxy-Delta(12,14)-prostaglandin J(2)) to Food and Drug Administration-approved thiazolidinedione drugs [pioglitazone (Actos) and rosiglitazone (Avandia)] for the treatment of diabetes. Once activated, PPARgamma will preferentially bind with retinoid X receptor alpha and signal antiproliferative, antiangiogenic, and prodifferentiation pathways in several tissue types, thus making it a highly useful target for down-regulation of carcinogenesis. Although PPAR-gamma activators show many anticancer effects on cell lines, their advancement into human advanced cancer clinical trials has met with limited success. This article will review translational findings in PPARgamma activation and targeting in carcinogenesis prevention as they relate to the potential use of PPARgamma activators clinically as cancer chemoprevention strategies.
Ondrey
Frank
F
Department of Otolaryngology and University of Minnesota Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota 55455, USA. ondre002@umn.edu
D000818:Animals; D045744:Cell Line, Tumor; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000494:pharmacology; D009369:Neoplasms / Q000517:prevention & control*; D009374:Neoplasms, Experimental / Q000517:prevention & control; D047495:PPAR gamma / Q000378:metabolism*; D047488:Retinoid X Receptors / Q000378:metabolism; D015398:Signal Transduction
D047908:Intracellular Signaling Peptides and Proteins; D047495:PPAR gamma; D047488:Retinoid X Receptors