The Key to Unlocking the Chemotherapeutic Potential of PPARγ Ligands: Having the Right Combination
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 therap...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2012/946943 |
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| author | Graham Skelhorne-Gross Christopher J. B. Nicol |
| author_facet | Graham Skelhorne-Gross Christopher J. B. Nicol |
| author_sort | Graham Skelhorne-Gross |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6a2650f546904f85b52360d161c614fa |
| institution | Kabale University |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-6a2650f546904f85b52360d161c614fa2025-02-03T01:11:12ZengWileyPPAR Research1687-47571687-47652012-01-01201210.1155/2012/946943946943The Key to Unlocking the Chemotherapeutic Potential of PPARγ Ligands: Having the Right CombinationGraham Skelhorne-Gross0Christopher J. B. Nicol1Department of Pathology and Molecular Medicine, Queen's University, Kingston, ON, K7L 3N6, CanadaDepartment of Pathology and Molecular Medicine, Queen's University, Kingston, ON, K7L 3N6, CanadaDespite 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.http://dx.doi.org/10.1155/2012/946943 |
| spellingShingle | Graham Skelhorne-Gross Christopher J. B. Nicol The Key to Unlocking the Chemotherapeutic Potential of PPARγ Ligands: Having the Right Combination PPAR Research |
| title | The Key to Unlocking the Chemotherapeutic Potential of PPARγ Ligands: Having the Right Combination |
| title_full | The Key to Unlocking the Chemotherapeutic Potential of PPARγ Ligands: Having the Right Combination |
| title_fullStr | The Key to Unlocking the Chemotherapeutic Potential of PPARγ Ligands: Having the Right Combination |
| title_full_unstemmed | The Key to Unlocking the Chemotherapeutic Potential of PPARγ Ligands: Having the Right Combination |
| title_short | The Key to Unlocking the Chemotherapeutic Potential of PPARγ Ligands: Having the Right Combination |
| title_sort | key to unlocking the chemotherapeutic potential of pparγ ligands having the right combination |
| url | http://dx.doi.org/10.1155/2012/946943 |
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