Glioma extracellular matrix molecules as therapeutic targets

Malignant gliomas which rarely metastasize, but are locally highly invasive into theextracellular matrix (ECM) microenvironment in the brain are difficult to treat. Despiteyears of research, current therapies including surgery, radiotherapy and chemotherapy areaimed at debulking of the brain tumor mass and targeting proliferating tumor cells. Thesetherapeutic approaches do not take into consideration the ECM, its composition and thechanges in ECM rigidity which can significantly affect glioma cell motility resulting intumor cell dissemination through the brain and establishment of new, distant tumor foci.Some ECM molecules such as metalloproteinases (MMPs) which are essential in matrixremodeling have been targeted therapeutically.However, due to the highly pleiotropic properties of MMPs, the outcomes of theclinical studies targeting these molecules have been disappointing and often resulted inincreased tumor growth. In addition, current therapies do not address the quiescentpopulation of the cancer stem cells which thrive in the ECM microenvironment of thevascular niche and are protected from therapeutic interventions. This chapter will focuson the review of the most recent information pertaining to the glioma extracellularmicroenvironment and identification of the possible biological targets within ECM foranti-glioma therapy.