Concerns about anti-angiogenic treatment in patients with glioblastoma multiforme

GBM can be roughly separated into an angiogenic component, and an invasive or migratory component. Although this latter component seems inert to anti-angiogenic therapy, it is of major importance for disease progression and survival. We reviewed all relevant literature. Published data support that clinical symptoms are tempered by anti-angiogenic treatment, but that tumour invasion continues. Unfortunately, current imaging modalities are affected by anti-angiogenic treatment too, making it even harder to define tumour margins. To illustrate this we present MRI, biopsy and autopsy specimens from bevacizumab-treated patients.Moreover, while treatment of other tumour types may be improved by combining chemotherapy with anti-angiogenic drugs, inhibiting angiogenesis in GBM may antagonise the efficacy of chemotherapeutic drugs by normalising the blood-brain barrier function.Although angiogenesis inhibition is of considerable value for symptom reduction in GBM patients, lack of proof of a true anti-tumour effect raises concerns about the place of this type of therapy in the treatment of GBM.The brain is the highest organised and most complex organ of the body. Some unique features of the brain that have an impact on the biology of brain tumours include extensive three-dimensional structuring with gray and white matter [1], and high density of blood capillaries making it a well-perfused organ; however, a blood-brain barrier (BBB) very selectively regulates the penetration of substances into the brain [2]. With respect to this specific micro-environment, brain cancer, in particular high-grade astrocytoma (malignant glioma, glioblastoma multiforme, GBM) differs from many other cancer types. Whereas this disease usually manifests itself as a focal lesion with central necrosis surrounded by an angiogenic tumour rim (one of the characteristics of GBM), this tumour also invades the surrounding extracellular matrix, using both white matter tracts and blood vessels as substrate [3