Vascular endothelial growth factor blockade: A potential new therapy in the management of cerebral arteriovenous malformations

Cerebral arteriovenous malformations (AVMs) occur universally in 1.1 per 100,000 people. These malformations are the cause of serious neurological morbidity or even death when they bleed. AVMs are not necessarily static congenital abnormalities. They can undergo internal changes due to angiogenesis resulting in vascular remodelling. They can even regrow after successful therapy. Vascular endothelial growth factors (VEGFs) play an important role in angiogenesis. Drugs that block the action of VEGF on vascular endothelial growth factor receptors (VEGFRs) on the endothelial cell surface are available. This blockade causes an anti-angiogenetic effect. Anti-angiogenic drugs are widely used as adjuvant therapy in the management of cancers because they suppress the formation of new blood vessels required by the tumour for growth. For similar reasons, they are used in the treatment of age-related macular degeneration.

The present treatment options for AVMs are surgery, embolisation and irradiation either on their own or in combination. Irradiation with stereotactic radiosurgery (SRS) offers the advantage of being non-invasive, but it relies on the late radiation effects to achieve its therapeutic goal of complete obliteration. This latent time (1–3 years), during which the risk for a bleed remains, is an inherent drawback of SRS. The histopathology of surgical specimens of post-SRS AVMs demonstrates a role of endothelial cells in repairing the radiation damage. Suppressing their activity post SRS by a VEGF blockade has the potential to enhance the radiation damage and hence speed up the obliteration process and reduce the latent time. It is postulated that such a ‘VEGF blockade’ could be useful as an adjuvant therapy to SRS. In addition, there is also the potential for a neo-adjuvant use, whereby a VEGF blockade could cause regression in the size of the AVM, making definite therapy easier. The rationale for the VEGF-blockade concept is presented and discussed.