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PPAR Research
Volume 2012, Article ID 946943, 13 pages
http://dx.doi.org/10.1155/2012/946943
Review Article

The Key to Unlocking the Chemotherapeutic Potential of PPARγ Ligands: Having the Right Combination

1Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, Canada K7L 3N6
2Cancer Biology and Genetics Division, Cancer Research Institute, Queen's University, Kingston, ON, Canada K7L 3N6
3Department of Biomedical and Molecular Sciences (Pharmacology and Toxicology), Queen's University, Kingston, ON, Canada K7L 3N6

Received 3 February 2012; Accepted 14 March 2012

Academic Editor: Yuji Kamijo

Copyright © 2012 Graham Skelhorne-Gross and Christopher J. B. Nicol. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Despite extensive preclinical evidence that peroxisome proliferator-activated receptor (PPAR)γ activation protects against tumourigenesis, results from a few clinical trials using PPARγ ligands as monotherapy show modest success. In spite of this, several groups reported exciting results with therapeutic regimens that combine PPARγ ligands with other compounds: chemotherapeutic agents, retinoid x receptor (RXR)α agonists, statins, or cell-to-cell signaling molecules in preclinical cancer models and human trials. Here we have compiled an extensive review, consolidating the existing literature, which overwhelmingly supports a beneficial effect of treating with PPARγ ligands in combination with existing chemotherapies versus their monotherapy in cancer. There are many examples in which combination therapy resulted in synergistic/additive effects on apoptosis, differentiation, and the ability to reduce cell growth and tumour burden. There are also studies that indicate that PPARγ ligand pretreatment overcomes resistance and reduces toxicities. Several mechanisms are explored to explain these protective effects. This paper highlights each of these studies that, collectively, make a very strong case for the use of PPARγ ligands in combination with other agents in the treatment and management of several cancers.