特别关注甲状腺癌—PPARγ激动剂的抗肿瘤作用

Title:Antineoplastic Effects of PPARγ Agonists, with a Special Focus on Thyroid Cancer

Volume: 23 Issue: 7

Author(s): Silvia Martina Ferrari, Gabriele Materazzi, Enke Baldini, Salvatore Ulisse, Paolo Miccoli, Alessandro Antonelli and Poupak Fallahi

Affiliation:

关键词: 过氧化物酶体增殖物激活受体-γ；噻唑烷二酮类;；PPARγ激动剂；抗肿瘤作用；甲状腺癌；分化型甲状腺癌；甲状腺未分化癌；

摘要: 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.

Cite this article as:

Silvia Martina Ferrari, Gabriele Materazzi, Enke Baldini, Salvatore Ulisse, Paolo Miccoli, Alessandro Antonelli and Poupak Fallahi , Antineoplastic Effects of PPARγ Agonists, with a Special Focus on Thyroid Cancer, Current Medicinal Chemistry 2016; 23 (7) . https://dx.doi.org/10.2174/0929867323666160203114607