title: Chemotherapy and chemoprevention by thiazolidinediones.
abstract: Thiazolidinediones (TZDs) are synthetic ligands of Peroxisome-Proliferator-Activated Receptor gamma (PPARγ). Troglitazone, rosiglitazone, and pioglitazone have been approved for treatment of diabetes mellitus type II. All three compounds, together with the first TZD ciglitazone, also showed an antitumor effect in preclinical studies and a beneficial effect in some clinical trials. This review summarizes hypotheses on the role of PPARγ in tumors, on cellular targets of TZDs, antitumor effects of monotherapy and of TZDs in combination with other compounds, with a focus on their role in the treatment of differentiated thyroid carcinoma. The results of chemopreventive effects of TZDs are also considered. Existing data suggest that the action of TZDs is highly complex and that actions do not correlate with cellular PPARγ expression status. Effects are cell-, species-, and compound-specific and concentration-dependent. Data from human trials suggest the efficacy of TZDs as monotherapy in prostate cancer and glioma and as chemopreventive agent in colon, lung, and breast cancer. TZDs in combination with other therapies might increase antitumor effects in thyroid cancer, soft tissue sarcoma, and melanoma.
authors: Internal Medicine, Department of Endocrinology, Metabolism, Nephrology and Clinical Chemistry, Department IV, University of Tuebingen, Otfried-Muellerstrasse 10, 72076 Tuebingen, Germany ; Center for Medical Research, Medical University of Graz, Stiftingtalstraße 24, 8010 Graz, Austria.
authors: Eleonore
authors: 0000-0002-6056-6829
authors: E
authors: Fröhlich
authors: Internal Medicine, Department of Endocrinology, Metabolism, Nephrology and Clinical Chemistry, Department IV, University of Tuebingen, Otfried-Muellerstrasse 10, 72076 Tuebingen, Germany.
authors: Richard
authors: 0000-0002-4817-382X
authors: R
authors: Wahl
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006801:Humans; D047495:PPAR gamma / Q000037:antagonists & inhibitors; D045162:Thiazolidinediones / Q000627:therapeutic use*; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*
chemical_list: D000970:Antineoplastic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones