Activation and Molecular Targets of Peroxisome Proliferator-Activated Receptor-gamma Ligands in Lung Cancer.
Lung cancer is the leading cause of cancer death, and five-year survival remains poor, raising the urgency for new treatment strategies. Activation of PPARgamma represents a potential target for both the treatment and prevention of lung cancer. Numerous studies have examined the effect of thiazolidinediones such as rosiglitazone and pioglitazone on lung cancer cells in vitro and in xenograft models. These studies indicate that activation of PPARgamma inhibits cancer cell proliferation as well as invasiveness and metastasis. While activation of PPARgamma can occur by direct binding of pharmacological ligands to the molecule, emerging data indicate that PPARgamma activation can occur through engagement of other signal transduction pathways, including Wnt signaling and prostaglandin production. Data, both from preclinical models and retrospective clinical studies, indicate that activation of PPARgamma may represent an attractive chemopreventive strategy. This article reviews the existing biological and mechanistic experiments focusing on the role of PPARgamma in lung cancer, focusing specifically on nonsmall cell lung cancer.
Division of Renal Diseases, Department of Medicine, School of Medicine, University of Colorado Denver, Denver, CO 80262, USA.
Raphael A
RA
Nemenoff
Mary
M
Weiser-Evans
Robert A
RA
Winn