PMC

An illustration demonstrating the pathways of primary and secondary GBMs.
Abbreviations: EGFR, epidermal growth factor receptor; PTEN, phosphatase and tensin homolog; LOH, loss of heterozygosity; TERT, telomerase reverse transcriptase; MGMT, O-6-methylguanine-DNA methyltransferase; CDKN2A/B, cyclin-dependent kinase inhibitor 2A/2B; NF1, neurofibromin 1; NES, nestin; MERTK, MER Proto-Oncogene, Tyrosine Kinase; ATRX, ATP-dependent helicase ATRX, X-linked helicase II; PDGFRA, platelet-derived growth factor receptor, alpha; CIC, capicua transcriptional repressor; FUBP1, far upstream element-binding protein 1.

Schematic representation of the effect of HIF on the progression of GBM. (A) Conventional anticancer therapies target the progenitor cells resulting in recurrence of tumor or resistance to the treatment. (B) Under hypoxic conditions, HIF level is upregulated, which leads to malignant progression of GBM by GSCs, thereby promoting angiogenesis and resistance to chemotherapy and radiotherapy. Targeting glioblastoma stem cells, NOTCH pathway, or downregulating the level of HIFs suppresses GBM growth by inhibiting GSCs that promotes differentiation and apoptosis and might be slower in regulating the tumor progression but provides a longer curative effect.