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Peroxisome proliferator-activated receptor γ in bladder cancer: A promising therapeutic target

Peroxisome Proliferator-Activated Receptors (PPARs) are ligand-activated intracellular transcription factors, members of the nuclear hormone receptor superfamily. The PPAR subfamily consist of three subtypes encoded by distinct genes denoted PPARα, PPARβ/δ, and PPARγ. The peroxisome proliferator-activated receptor γ (PPARγ) is the most extensively studied subtype of the PPARs. Over the last decade, research on PPARγ unveiled its role in important biological processes, including lipid biosynthesis, glucose metabolism, anti-inflammatory response, and atherosclerosis. Recently, PPARγ has been shown to be expressed in many cancers including, lung, prostate, bladder, colon, breast, duodenal, thyroid, and has been demonstrated to potentially play an important role in carcinogenesis. In bladder cancer, PPARγ ligands such as troglitazone and 15d-PGJ2 have shown to inhibit tumor growth. We have recently published the first report to show that a new class of PPARγ agonists, PPARγ-active C-DIMs, which are more potent than the previous generation of drugs, exhibit anti-tumorigenic activity against bladder cancer cells in vitro and bladder tumors in vivo. The following review will discuss the molecular structure of PPARγ, its function, and its role in cancer biology and how it is emerging as a promising therapeutic target in bladder cancer.