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Current Cancer Drug Targets

Editor-in-Chief

ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Review Article

PPARγ Agonists in Combination Cancer Therapies

Author(s): Piotr Mrowka and Eliza Glodkowska-Mrowka*

Volume 20, Issue 3, 2020

Page: [197 - 215] Pages: 19

DOI: 10.2174/1568009619666191209102015

Price: $65

Abstract

Peroxisome proliferator-activated receptor-gamma (PPARγ) is a nuclear receptor acting as a transcription factor involved in the regulation of energy metabolism, cell cycle, cell differentiation, and apoptosis. These unique properties constitute a strong therapeutic potential that place PPARγ agonists as one of the most interesting and widely studied anticancer molecules.

Although PPARγ agonists exert significant, antiproliferative and tumoricidal activity in vitro, their anticancer efficacy in animal models is ambiguous, and their effectiveness in clinical trials in monotherapy is unsatisfactory. However, due to pleiotropic effects of PPARγ activation in normal and tumor cells, PPARγ ligands interact with many antitumor treatment modalities and synergistically potentiate their effectiveness. The most spectacular example is a combination of PPARγ ligands with tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML). In this setting, PPARγ activation sensitizes leukemic stem cells, resistant to any previous form of treatment, to targeted therapy. Thus, this combination is believed to be the first pharmacological therapy able to cure CML patients.

Within the last decade, a significant body of data confirming the benefits of the addition of PPARγ ligands to various antitumor therapies, including chemotherapy, hormonotherapy, targeted therapy, and immunotherapy, has been published. Although the majority of these studies have been carried out in vitro or animal tumor models, a few successful attempts to introduce PPARγ ligands into anticancer therapy in humans have been recently made. In this review, we aim to summarize shines and shadows of targeting PPARγ in antitumor therapies.

Keywords: Peroxisome proliferator-activated receptor-gamma, PPARγ ligand, thiazolidinediones, cancer, leukemia, combination therapy, tyrosine kinase inhibitors, imatinib.

Graphical Abstract

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