title: Strategies to improve delivery of anticancer drugs across the blood-brain barrier to treat glioblastoma.
abstract: Glioblastoma (GBM) is a lethal and aggressive brain tumor that is resistant to conventional radiation and cytotoxic chemotherapies. Molecularly targeted agents hold great promise in treating these genetically heterogeneous tumors, yet have produced disappointing results. One reason for the clinical failure of these novel therapies can be the inability of the drugs to achieve effective concentrations in the invasive regions beyond the bulk tumor. In this review, we describe the influence of the blood-brain barrier on the distribution of anticancer drugs to both the tumor core and infiltrative regions of GBM. We further describe potential strategies to overcome these drug delivery limitations. Understanding the key factors that limit drug delivery into brain tumors will guide future development of approaches for enhanced delivery of effective drugs to GBM.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (R.K.O., K.E.P., R.K.M., W.F.E.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (T.T.S., J.N.S.).
authors.forename: Rajneet K
authors.initials: RK
authors.lastname: Oberoi
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (R.K.O., K.E.P., R.K.M., W.F.E.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (T.T.S., J.N.S.).
authors.forename: Karen E
authors.initials: KE
authors.lastname: Parrish
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (R.K.O., K.E.P., R.K.M., W.F.E.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (T.T.S., J.N.S.).
authors.forename: Terence T
authors.initials: TT
authors.lastname: Sio
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (R.K.O., K.E.P., R.K.M., W.F.E.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (T.T.S., J.N.S.).
authors.forename: Rajendar K
authors.initials: RK
authors.lastname: Mittapalli
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (R.K.O., K.E.P., R.K.M., W.F.E.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (T.T.S., J.N.S.).
authors.forename: William F
authors.initials: WF
authors.lastname: Elmquist
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota (R.K.O., K.E.P., R.K.M., W.F.E.); Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (T.T.S., J.N.S.).
authors.forename: Jann N
authors.initials: JN
authors.lastname: Sarkaria
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001932:Brain Neoplasms / Q000188:drug therapy*; D016503:Drug Delivery Systems / Q000295:instrumentation* / Q000379:methods*; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans
chemical_list: D000970:Antineoplastic Agents
keywords: blood-brain barrier; drug delivery; efflux transporters; glioma