Glioblastoma (GBM), the most common primary malignant brain tumor in adults, is associated with significant morbidity and mortality despite maximal safe resection followed by chemo- and radiotherapy. GBMs contain self-renewing, tumorigenic glioma stem cells that contribute to tumor initiation, heterogeneity, therapeutic resistance, and recurrence. Intratumoral heterogeneity (ITH) of GBMs is also a major contributing factor to poor clinical outcomes associated with these high-grade glial tumors. Herein, the authors summarize recent discoveries and advances in the molecular and phenotypic characterization of GBMs with particular focus on ITH. In so doing, they attempt to highlight recent advances in molecular signatures/properties and metabolic alterations in an effort to clarify translational implications that may ultimately improve clinical outcomes.
Keywords: CIMP+ = CIMP positive; CIMP− = CpG island methylator phenotype negative; EGFR = epidermal growth factor receptor; GBM; GBM = glioblastoma; GSC; GSC = glioma stem cell; IDH = isocitrate dehydrogenase; ITH = intratumoral heterogeneity; NSC = neural stem cell; SVZ = subventricular zone; experimental therapeutics; glioblastoma; glioma stem cells; intratumoral heterogeneity; oncology.