Advances in the targeting of HIF-1α and future therapeutic strategies for glioblastoma multiforme

Cell metabolism can be reprogrammed by tissue hypoxia leading to cell transformation and glioblastoma multiforme (GBM) progression. In response to hypoxia, GBM cells are able to express a transcription factor called hypoxia inducible factor-1 (HIF-1). HIF-1 belongs to a family of heterodimeric proteins that includes HIF-1 alpha and HIF-1 beta subunits. HIF-1 alpha has been reported to play a pivotal role in GBM development and progression. In the present review, we discuss the role of HIF-1 alpha in glucose uptake, cancer proliferation, cell mobility and chemoresistance in GBM. Evidence from previous studies indicates that HIF-1 alpha regulates angiogenesis, metabolic and transcriptional signaling pathways. Examples of such are the EGFR, PI3K/Akt and MAPK/ERK pathways. It affects cell migration and invasion by regulating glucose metabolism and growth in GBM cells. The present review focuses on the strategies through which to target HIF-1 alpha and the related downstream genes highlighting their regulatory roles in angiogenesis, apoptosis, migration and glucose metabolism for the development of future GBM therapeutics. Combined treatment with inhibitors of HIF-1 alpha and glycolysis may enhance antitumor effects in clinical settings.