Improving drug delivery to primary and metastatic brain tumors: strategies to overcome the blood-brain barrier

Abstract

Brain tumor diagnosis has an extremely poor prognosis, due in part to the blood-brain barrier (BBB) that prevents both early diagnosis and effective drug delivery. The infiltrative nature of primary brain tumors and the presence of micro-metastases lead to tumor cells that reside behind an intact BBB. Recent genomic technologies have identified many genetic mutations present in glioma and other central nervous system (CNS) tumors, and this information has been instrumental in guiding the development of molecularly targeted therapies. However, the majority of these agents are unable to penetrate an intact BBB, leading to one mechanism by which the invasive brain tumor cells effectively escape treatment. The diagnosis and treatment of a brain tumor remains a serious challenge and new therapeutic agents that either penetrate the BBB or disrupt mechanisms that limit brain penetration, such as endothelial efflux transporters or tight junctions, are required in order to improve patient outcomes in this devastating disease.