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

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
• glioblastoma
• malignant glioma
• anti-angiogenesis
• VEGF
• bevacizumab
• neuro-oncology
• personalized medicine

Article Highlights

• Glioblastoma multiforme is the most common primary malignant brain tumor in adults.

• Current standard of care improves survival only to about 14 months.

• Angiogenesis is a hallmark characteristic of glioblastoma, making it an appealing target for treatment development.

• Bevacizumab is the most studied antiangiogenic agent and the only FDA-approved second-line treatment.

• The use of antiangiogenic agents in glioblastoma has evolved into a role focused on symptom control, since earlier studies failed to gain support for efficacy as a purely cytotoxic agent in more recent higher class studies.

Current studies focus on combination treatments with antiangiogenic therapies for glioblastoma.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.