Angiogenesis in brain tumours

Top Cited Papers
Publisher Website
Google Scholar
Abstract
The growth of both primary and metastatic brain tumours depends on their ability to recruit blood vessels by co-opting the host vessels (co-option), forming new vessels by sprouting (angiogenesis) and/or by recruiting bone-marrow-derived cells (vasculogenesis). Of primary malignant brain tumours, glioblastoma is the most common and is uniformly fatal. Malignant glioma vessels are highly abnormal, both structurally and functionally. This abnormality contributes to high interstitial fluid pressure, hypoxia and brain oedema. Vascular endothelial growth factor (VEGF) has a major role in neovascularization, but other molecules are also involved and might be important therapeutic targets. In preclinical models of brain tumours, anti-angiogenesis therapy can transiently prune and normalize the tumour vasculature and improve the outcome of radiation and/or chemotherapy given during the normalization window. This window has also been demonstrated in patients with recurrent glioblastoma using new MRI techniques that allow structural and functional evaluation of blood vessels during tumour growth and treatment. Anti-VEGF therapy has so far shown promising results in small clinical trials, with increased response rates and alleviation of oedema. Larger trials of anti-VEGF agents and other therapeutics (for example, rapamycin or blockers of αvβ3 integrin) are ongoing or being planned. A number of randomized phase II and III trials are examining the effect of anti-angiogenic therapy in combination with radiation and chemotherapy in patients with brain tumours. Imaging and blood biomarkers may be helpful in evaluating tumour response to, and toxicity from, these agents. It should be noted that anti-VEGF agents have rare but serious side effects on the CNS, such as intracerebral haemorrhage.