The evolving role of antiangiogenic therapies in glioblastoma multiforme: current clinical significance and future potential

Expert Opin Investig Drugs. 2019 Sep;28(9):787-797. doi: 10.1080/13543784.2019.1650019. Epub 2019 Aug 20.

Abstract

Introduction: Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor in adults, but its prognosis remains poor despite significant advances in our understanding of its molecular biology and investigation of numerous treatment modalities. Despite conventional treatment consisting of surgical resection, radiotherapy, and temozolomide marginally prolonging survival, most GBM patients die within 2 years of initial diagnosis. Bevacizumab (Bev) is the best-studied antiangiogenic agent for GBM and currently the only FDA-approved second-line treatment. Areas covered: Areas covered in this review include the molecular pathways of angiogenesis in glioblastoma, specifically the overexpression of vascular endothelial growth factor (VEGF) and robust formation of tumor neovasculature. In addition, this review covers pharmacological targeting of this process as a longstanding attractive clinical strategy, specifically by Bev. Expert opinion: This review attempts to discuss the history of early studies of antiangiogenic treatment for GBM that eventually failed in subsequent studies and the evolving modern role of Bev in the course of treatment for a variety of indications, including symptom control, reduced glucocorticoid use, and improved quality of life.

Keywords: GBM; VEGF; anti-angiogenesis; bevacizumab; glioblastoma; malignant glioma; neuro-oncology; personalized medicine.

Publication types

  • Review

MeSH terms

  • Adult
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Brain Neoplasms / blood supply
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Glioblastoma / blood supply
  • Glioblastoma / drug therapy*
  • Glioblastoma / pathology
  • Humans
  • Molecular Targeted Therapy
  • Neovascularization, Pathologic / drug therapy
  • Neovascularization, Pathologic / pathology
  • Prognosis
  • Quality of Life
  • Vascular Endothelial Growth Factor A / genetics

Substances

  • Angiogenesis Inhibitors
  • Vascular Endothelial Growth Factor A