title: The blood-brain barrier and cancer: transporters, treatment, and Trojan horses.
abstract: Despite scientific advances in understanding the causes and treatment of human malignancy, a persistent challenge facing basic and clinical investigators is how to adequately treat primary and metastatic brain tumors. The blood-brain barrier is a physiologic obstruction to the delivery of systemic chemotherapy to the brain parenchyma and central nervous system (CNS). A number of physiologic properties make the endothelium in the CNS distinct from the vasculature found in the periphery. Recent evidence has shown that a critical aspect of this barrier is composed of xenobiotic transporters which extrude substrates from the brain into the cerebrospinal fluid and systemic circulation. These transporters also extrude drugs and toxins if they gain entry into the cytoplasm of brain endothelial cells before they enter the brain. This review highlights the properties of the blood-brain barrier, including the location, function, and relative importance of the drug transporters that maintain this barrier. Primary and metastatic brain malignancy can compromise this barrier, allowing some access of chemotherapy treatment to reach the tumor. The responsiveness of brain tumors to systemic treatment found in past clinical research is discussed, as are possible explanations as to why CNS tumors are nonetheless able to evade therapy. Finally, strategies to overcome this barrier and better deliver chemotherapy into CNS tumors are presented.
authors.affiliation: Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC 20007, USA. deekenj@georgetown.edu
authors.forename: John F
authors.initials: JF
authors.lastname: Deeken
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Löscher
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001812:Blood-Brain Barrier / Q000502:physiology* / Q000528:radiation effects; D001932:Brain Neoplasms / Q000378:metabolism / Q000556:secondary / Q000628:therapy*; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D026901:Membrane Transport Proteins / Q000502:physiology*; D008954:Models, Biological; D011878:Radiotherapy
chemical_list: D000970:Antineoplastic Agents; D026901:Membrane Transport Proteins