Targeting Glioblastoma Stem Cells (GSCs) with Peroxisome Proliferator-activated Receptor Gamma (PPARγ) Ligands

Glioblastoma multiforme (GBM), also known as glioblastoma, is the most common and aggressive brain tumor. GBM has a poor survival rate and high resistance to standard therapy, leading to recurrence and metastasis to adjacent normal regions. Glioblastoma stem cells (GSCs) are regarded as an emerging target for therapy of GBM. Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a nuclear receptor that functions in a variety of cancers and in normal adipocyte differentiation. The newly discovered connection between PPAR gamma ligands and cancer stem cells (CSCs) raises important implications for the potential therapeutic use of synthetic PPAR gamma ligands, such as thiazolidinediones (TZDs), in glioblastoma. Here, I hypothesize that synthetic PPAR gamma ligands serve to modulate stemness-related molecules and several signaling pathway in GSCs and I propose potential experimental approaches to investigate the effects of these ligands on GSCs in vitro and in vivo.