Abstract

Despite aggressive surgery, radiotherapy and chemotherapy, malignant gliomas remain uniformly fatal. To progress, these tumours stimulate the formation of new blood vessels through processes driven primarily by vascular endothelial growth factor (VEGF). However, the resulting vessels are structurally and functionally abnormal, and contribute to a hostile microenvironment (low oxygen tension and high interstitial fluid pressure) that selects for a more malignant phenotype with increased morbidity and mortality. Emerging preclinical and clinical data indicate that anti-VEGF therapies are potentially effective in glioblastoma — the most frequent primary brain tumour — and can transiently normalize tumour vessels. This creates a window of opportunity for optimally combining chemotherapeutics and radiation.

Author affiliations

1. Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, 100 Blossom Street, Boston, Massachusetts 02114, USA.
2. A.A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, 100 Blossom Street, Boston, Massachusetts 02114, USA.
3. Stephen E. and Catherine Pappas Center for Neuro-Oncology, Massachusetts General Hospital and Harvard Medical School, 100 Blossom Street, Boston, Massachusetts 02114, USA.

Correspondence to: Rakesh K. Jain¹ Email: jain@steele.mgh.harvard.edu

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