Treatment of Anaplastic Thyroid Cancer: Is there a Role for PPARγ Agonists?

Alessandro      Antonelli; Silvia   M.   Ferrari; Poupak      Fallahi; Piero      Berti; Gabriele      Materazzi; Emiliano      Ghiri; Angelo      Carpi; Andrea      Nicolini; Paolo      Miccoli

Abstract

The medical treatment of patients diagnosed with anaplastic thyroid cancer (ATC) is not standardized, and it is almost always used in combination with surgery. Novel treatment strategies are necessary to make progresses in treating ATC. Promising future directives include the possibility offered by peroxisome proliferator-activated receptor γ (PPARγ) agonists. PPARγ are members of a superfamily of nuclear hormone receptors. Activation of PPARγ isoforms elicits both antineoplastic and anti-inflammatory effects in several types of mammalian cells. Ligands for PPARγ induce apoptosis and exert antiproliferative effects on several carcinoma cell lines, and PPARγ agonists inhibit cell growth of some types of human thyroid cancer. We have recently evaluated the antiproliferative effect of PPARγ agonists in primary cultured cells from human ATC (ANA) patients. The results of this study demonstrated that PPARγ ligands thiazolidinediones (TZD) exert a significant antiproliferative effect in primary ATC cells, therefore TZD could be promising therapeutic agents for the treatment of patients who fails to respond to traditional treatments. The use of antiproliferative tests in ANA cells obtained from each patient may help in detecting responsive patients, in preventing the administration of inactive drugs to those unresponsive, and in comparing the antiproliferative effect of different drugs. This article also reviews some patents related to the field.

Keywords: Anaplastic thyroid cancer, thyroid cancer, primary thyroid cancer cell cultures, PPARγ agonists, thiazolidinediones

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