title: Antineoplastic Effects of PPARγ Agonists, with a Special Focus on Thyroid Cancer.
abstract: Peroxisome Proliferator-Activated Receptor-γ (PPARγ) is a ligand-activated nuclear hormone receptor that functions as transcription factor and plays an important role in lipid metabolism and insulin sensitization. Recent studies have shown that PPARγ is overexpressed in many tumor types, including cancers of breast, lung, pancreas, colon, glioblastoma, prostate and thyroid differentiated/anaplastic cancers. These data suggest a role of PPARγ in tumor development and/or progression. PPARγ is emerging as a growth-limiting and differentiation-promoting factor, and it exerts a tumor suppressor role. Moreover, naturally-occurring and synthetic PPARγ agonists promote growth inhibition and apoptosis. Thiazolidinediones (TZDs) are synthetic agonists of PPARγ that were developed to treat type II diabetes. These compounds also display anticancer effects which appear mainly to be independent of their PPARγ agonist activity. Various preclinical and clinical studies strongly suggest a role for TZDs both alone and in combination with existing chemotherapeutic agents, for the treatment of cancer. Differentiation therapy involves the use of agents with the ability to induce differentiation in cells that have lost this ability, i.e. cancer cells, targeting pathways capable of re-activating blocked terminal differentiation programs. PPARγ agonists have been shown to induce differentiation in solid tumors such as thyroid differentiated/ anaplastic cancers and sarcomas. However, emerging data suggest that chronic use of TZDs is associated with increased risk of adverse cardiovascular events. The exploration of newer PPARγ agonists can help in unveiling the underlying mechanisms of these drugs, providing new molecules that are able to treat cancer, without increasing the cardiovascular risk of neoplastic patients.
authors: Silvia Martina
authors: SM
authors: Ferrari
authors: Gabriele
authors: G
authors: Materazzi
authors: Enke
authors: E
authors: Baldini
authors: Salvatore
authors: S
authors: Ulisse
authors: Paolo
authors: P
authors: Miccoli
authors: Department of Clinical and Experimental Medicine, University of Pisa, Via Savi, 10, 56126, Pisa, Italy. alessandro.antonelli@med.unipi.it.
authors: Alessandro
authors: A
authors: Antonelli
authors: Poupak
authors: P
authors: Fallahi
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D047495:PPAR gamma