Malignant Glioma Physiology: Cellular Response to Hypoxia and Its Role in Tumor Progression

Clinical Principles

Malignant gliomas occur primarily in patients 40 to 70 years of age.

Clinical presentation depends on tumor location and can include headache, seizures, or mental status changes.

Age, functional status at presentation, and seizures are important predictors of outcome.

Therapeutic options include aggressive surgery, but since resection alone is not often curative, adjunctive therapy is warranted.

Patients with glioblastoma multiforme have a median survival of 50 weeks.

Pathophysiologic Principles

Microvascular proliferation in glioblastoma multiforme is a form of angiogenesis associated with neoplastic progression.

Vascular proliferation is often noted in hypoxic regions associated with necrosis and is due at least in part to hypoxia-inducible factor–mediated expression of vascular endothelial growth factor in hypoxic zones.

Losses of tumor suppressor genes, such as TP53 and PTEN, and activation of oncogenes, including EGFR and PDGFR, may directly or indirectly modulate hypoxia-inducible factor-1–mediated gene expression in a manner favoring new vessel growth.

Angiogenesis and hypoxia-inducible factor-1–mediated gene expression are natural targets for interventions since they consistently occur during the progression of glioblastoma multiforme.