New molecular targets in angiogenic vessels of glioblastoma tumours

Abstract

Antiangiogenesis approaches have the potential to be particularly effective in the treatment of glioblastoma tumours. These tumours exhibit extremely high levels of neovascularisation, which may contribute to their extremely aggressive behaviour, not only by providing oxygenation and nutrition, but also by establishing a leaky vasculature that lacks a blood-brain barrier. This leaky vasculature enables migration of tumour cells, as well as the build up of fluid, which exacerbates tissue damage due to increased intracranial pressure. Here, we discuss the considerable progress that has been made in the identification of the pro- and antiangiogenic factors produced by glioblastoma tumours and the effects of these molecules in animal models of the disease. The safety and efficacy of some of these approaches have now been demonstrated in clinical trials. However, the ability of tumours to overcome these therapies and to re-establish angiogenesis requires further clinical research regarding potential multimodality therapies, as well as basic research into the regulation of angiogenesis by as yet unidentified factors. Optimisation of noninvasive procedures for monitoring of angiogenesis would greatly facilitate such research.

Fig. 1. Examples of Endogenous Inhibitors of Angiogenesis in the Normal Brain or GBM Tumors: The Cell of Origin or Cellular Localization

Angiostatin, endorepellin and endostatin are proteolytic cleavage products. Various cells produce proteases but the relative contribution of each of these cellular sources of proteases to the generation of these cleavage products has not yet been defined.

Fig. 2. Examples of Localized Angiogenic Targets in GBM Tumors

A schematic of the new targets of anti-angiogenic therapy, as discussed in the text, in the neovasculature of GBM tumors.