Glioblastoma (GBM) is the most common primary brain tumor and carries a grave prognosis. Despite years of research investigating potentially new therapies for GBM, the median survival rate of individuals with this disease has remained fairly stagnant. Delivery of drugs to the tumor site is hampered by various barriers posed by the GBM pathological process and by the complex physiology of the blood-brain and blood-cerebrospinal fluid barriers. These anatomical and physiological barriers serve as a natural protection for the brain and preserve brain homeostasis, but they also have significantly limited the reach of intraparenchymal treatments in patients with GBM. In this article, the authors review the functional capabilities of the physical and physiological barriers that impede chemotherapy for GBM, with a specific focus on the pathological alterations of the blood-brain barrier (BBB) in this disease. They also provide an overview of current and future methods for circumventing these barriers in therapeutic interventions. Although ongoing research has yielded some potential options for future GBM therapies, delivery of chemotherapy medications across the BBB remains elusive and has limited the efficacy of these medications.
Keywords: BBB = blood-brain barrier; BCSFB = blood–cerebrospinal fluid barrier; BTB = blood-tumor barrier; BV = bevacizumab; CNS = central nervous system; CSC = cancer stem-like cell; CSF = cerebrospinal fluid; GBM = glioblastoma; Gliadel; LTH = liposomal Trojan horse; TMZ = temozolomide; VEGF = vascular endothelial growth factor; blood-brain barrier; blood-tumor barrier; glioblastoma; liposome; mannitol; nanoparticle; stem cell; thermotherapy; ultrasound.