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Pioglitazone (ACTOS) is a thiazolidinedione for peroxisome proliferator-activated receptor γ (PPAR-γ) that has been well established for the second or third line treatment of type 2 diabetes mellitus. Beyond the effects on glucose metabolism, pioglitazone displays positive effects on lipid metabolism, blood pressure, endothelial function, bone density, and apoptosis of cancer cells. In fact, according to in vitro experiments and preclinical studies, PPAR-γ ligand is currently considered a potential target for both chemoprevention and cancer therapy. PPAR-γ ligands are known to inhibit cancer cell proliferation and metastasis through terminal differentiation and underexpression of inflammatory mediators. Despite its anticancer properties, pioglitazone was withdrawn by the national medicine agencies of France and Germany, due to reports of increased incidence of bladder cancer. These reports were associated with European populations undergoing higher doses and longer durations of treatment. In this review, we discuss the pharmacokinetics, therapeutic potential, and limitations regarding the clinical use of pioglitazone, with a focus on cancer treatment.
Vasileiou et al. (Thu,) studied this question.