Antiangiogenic therapy for glioblastoma: current status and future prospects

Clin Cancer Res. 2014 Nov 15;20(22):5612-9. doi: 10.1158/1078-0432.CCR-14-0834.


Glioblastoma is characterized by high expression levels of proangiogenic cytokines and microvascular proliferation, highlighting the potential value of treatments targeting angiogenesis. Antiangiogenic treatment likely achieves a beneficial impact through multiple mechanisms of action. Ultimately, however, alternative proangiogenic signal transduction pathways are activated, leading to the development of resistance, even in tumors that initially respond. The identification of biomarkers or imaging parameters to predict response and to herald resistance is of high priority. Despite promising phase II clinical trial results and patient benefit in terms of clinical improvement and longer progression-free survival, an overall survival benefit has not been demonstrated in four randomized phase III trials of bevacizumab or cilengitide in newly diagnosed glioblastoma or cediranib or enzastaurin in recurrent glioblastoma. However, future studies are warranted. Predictive markers may allow appropriate patient enrichment, combination with chemotherapy may ultimately prove successful in improving overall survival, and novel agents targeting multiple proangiogenic pathways may prove effective.

Publication types

  • Editorial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers / metabolism
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Clinical Trials as Topic
  • Diagnostic Imaging
  • Drug Resistance, Neoplasm
  • Glioblastoma / diagnosis
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • Neovascularization, Pathologic / diagnosis
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / metabolism


  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Biomarkers