The potential for remodelling the tumour vasculature in glioblastoma

Abstract

Despite significant improvements in the clinical management of glioblastoma, poor delivery of systemic therapies to the entire population of tumour cells remains one of the biggest challenges in the achievement of more effective treatments. On the one hand, the abnormal and dysfunctional tumour vascular network largely limits blood perfusion, resulting in an inhomogeneous delivery of drugs to the tumour. On the other hand, the presence of an intact blood-brain barrier (BBB) in certain regions of the tumour prevents chemotherapeutic drugs from permeating through the tumour vessels and reaching the diseased cells. In this review we analyse in detail the implications of the presence of a dysfunctional vascular network and the impenetrable BBB on drug transport. We discuss advantages and limitations of the currently available strategies for remodelling the tumour vasculature aiming to ameliorate the above mentioned limitations. Finally we review research methods for visualising vascular dysfunction and highlight the power of DCE- and DSC-MRI imaging to assess changes in blood perfusion and BBB permeability.

Keywords: Blood-brain barrier; Glioblastoma; MRI; Tumour remodelling; Vasculature permeability.