Using the molecular classification of glioblastoma to inform personalized treatment

J Pathol. 2014 Jan;232(2):165-77. doi: 10.1002/path.4282.

Abstract

Glioblastoma is the most common and most aggressive diffuse glioma, associated with short survival and uniformly fatal outcome, irrespective of treatment. It is characterized by morphological, genetic and gene-expression heterogeneity. The current standard of treatment is maximal surgical resection, followed by radiation, with concurrent and adjuvant chemotherapy. Due to the heterogeneity, most tumours develop resistance to treatment and shortly recur. Following recurrence, glioblastoma is quickly fatal in the majority of cases. Recent genetic molecular advances have contributed to a better understanding of glioblastoma pathophysiology and disease stratification. In this paper we review basic glioblastoma pathophysiology, with emphasis on clinically relevant genetic molecular alterations and potential targets for further drug development.

Keywords: 1p/19q; EGFR; FGFR; IDH; MGMT; TACC; glioblastoma; mesenchymal; pathogenesis; proneural.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / genetics*
  • Brain Neoplasms / classification
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Drug Discovery*
  • Drug Resistance, Neoplasm
  • Genetic Predisposition to Disease
  • Glioblastoma / classification
  • Glioblastoma / drug therapy*
  • Glioblastoma / genetics
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • Molecular Targeted Therapy
  • Patient Selection
  • Phenotype
  • Precision Medicine*
  • Signal Transduction / drug effects

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor