Peroxisome proliferator-activated receptor gamma and lung cancer biology: implications for therapy

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor family of transcriptional modulators. In addition to their known roles in regulation of metabolism and inflammation, PPARs have also been implicated in carcinogenesis based on studies showing their ability to modulate cellular differentiation, proliferation, and apoptosis. Of the 3 PPARs identified to date (PPARalpha, PPARbeta/delta, and PPARgamma), PPARgamma has been studied the most in part because of the availability of PPARgamma agonists (also known as PPARgamma ligands). In many tumor cells, including lung carcinoma cells, activation of PPARgamma results in decreased cellular proliferation; this is particularly true for non-small cell lung carcinoma, the most common malignant lung tumor in the United States. Studies performed in xenograft models of lung cancer also show decreased tumor growth and progression in animals treated with PPARgamma ligands. More recently, data are emerging from retrospective clinical studies that suggest a protective role for PPARgamma ligands on the incidence of lung cancer. This review summarizes the available data that implicate PPARs in lung carcinogenesis while focusing on PPARgamma as a potential target for the development of novel anti-lung cancer treatment strategies.