We have recently shown that PPARα gene and protein expression is increased in glioblastoma and has independent clinical prognostic significance in multivariate analyses.
Therefore, PPARα antagonism arises as a potent new strategy as adjuvant to gold standard therapies for GB for counteracting recurrences and opening the way for pre-clinical trials for this class of compounds.
In this work, we used a new PPARα antagonist on patient-derived GB primary cells, with particular focus on the effects on lipid metabolism and response to radiotherapy.
Further studies are required to explore genetic associations with high PPARA expression and to analyse the predictive role of PPARα expression in glioblastoma models in response to PPARα agonists.
Fenofibrate-induced PPARα transcriptional activity is expected to shift energy metabolism from glycolysis to fatty acid β-oxidation, which in the long-term, could target weak metabolic points of glycolysis-dependent glioblastoma cells.
Previously we reported that the peroxisome proliferator-activated receptor alpha/gamma dual ligand TZD18 inhibited growth and induced apoptosis of leukemia and glioblastoma cells.
Expression of this gene in human glioblastoma T98G cells was strongly down regulated after treatment with clofibrate or Wy-14,643, two PPARalpha agonists.