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Updated: May 1, 2026
Translational Orthotopic Models of Glioblastoma Multiforme
Published on: February 17, 2023
Biological Rationale for the Use of PPARγ Agonists in Glioblastoma
Hayley Patricia Ellis1, Kathreena Mary Kurian2
1School of Cellular and Molecular Medicine, University of Bristol , Bristol , UK.
Abstract:
Glioblastoma multiforme (GBM) is the most common primary intrinsic central nervous system tumor and has an extremely poor overall survival with only 10% patients being alive after 5 years. There has been interesting preliminary evidence suggesting that diabetic patients receiving peroxisome proliferator-activated receptor gamma (PPARγ) agonists, a group of anti-diabetic, thiazolidinedione drugs, have an increased median survival for glioblastoma. Although thiazolidinediones are effective oral medications for type 2 diabetes, certain agonists carry the risk for congestive heart failure, myocardial infarction, cardiovascular disease, bone loss, weight gain, and fluid retention as side-effects. The nuclear receptor transcription factor PPARγ has been found to be expressed in high grade gliomas, and its activation has been shown to have several antineoplastic effects on human and rat glioma cell lines, and in some instances an additional protective increase in antioxidant enzymes has been observed in normal astrocytes. At present, no clinical trials are underway with regards to treating glioma patients using PPARγ agonists. This review presents the case for evaluating the potential of PPARγ agonists as novel adjuvants in the treatment of refractory high grade glioma.
Insights
Peroxisome proliferator-activated receptor gamma (PPARγ) agonists, used for diabetes, may improve survival in glioblastoma patients. Further research is needed to explore their potential as adjuvant cancer therapy.
Area of Science:
- Neuro-oncology
- Endocrinology
- Pharmacology
Background:
- Glioblastoma multiforme (GBM) is an aggressive brain tumor with poor prognosis.
- Preliminary evidence suggests a survival benefit for glioblastoma patients using peroxisome proliferator-activated receptor gamma (PPARγ) agonists.
- PPARγ is expressed in high-grade gliomas and its activation shows antineoplastic effects.
Purpose of the Study:
- To review the potential of PPARγ agonists as novel adjuvant therapy for high-grade glioma.
- To highlight the antineoplastic and protective effects of PPARγ activation.
Main Methods:
- Literature review of studies on PPARγ agonists and glioma.
- Analysis of preclinical data on PPARγ activation in glioma cell lines.
- Examination of potential side effects of thiazolidinedione drugs.
Main Results:
- PPARγ agonists, a class of anti-diabetic drugs (thiazolidinediones), show preliminary promise in glioblastoma survival.
- PPARγ activation exhibits antineoplastic effects in glioma models and may increase protective antioxidant enzymes in astrocytes.
- Known side effects of thiazolidinediones include cardiovascular risks and fluid retention.
Conclusions:
- PPARγ agonists warrant investigation as a potential adjuvant treatment for refractory high-grade glioma.
- Clinical trials are currently lacking but are needed to validate the efficacy and safety of PPARγ agonists in glioma patients.
