Strategies to improve delivery of anticancer drugs across the blood-brain barrier to treat glioblastoma

Rajneet K. Oberoi; Karen E. Parrish; Terence T. Sio; Rajendar K. Mittapalli; William F. Elmquist; Jann N. Sarkaria

doi:10.1093/neuonc/nov164

Strategies to improve delivery of anticancer drugs across the blood-brain barrier to treat glioblastoma

Rajneet K. Oberoi, Karen E. Parrish, Terence T. Sio, Rajendar K. Mittapalli, William F. Elmquist, Jann N. Sarkaria

Radiation Oncology

Research output: Contribution to journal › Review article › peer-review

117 Scopus citations

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.

Original language	English (US)
Pages (from-to)	27-36
Number of pages	10
Journal	Neuro-oncology
Volume	18
Issue number	1
DOIs	https://doi.org/10.1093/neuonc/nov164
State	Published - Jan 1 2016

Keywords

blood-brain barrier
drug delivery
efflux transporters
glioma

ASJC Scopus subject areas

Oncology
Clinical Neurology
Cancer Research

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10.1093/neuonc/nov164

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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.",

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AU - Elmquist, William F.

AU - Sarkaria, Jann N.

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N2 - 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.

AB - 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.

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Strategies to improve delivery of anticancer drugs across the blood-brain barrier to treat glioblastoma

Abstract

Keywords

ASJC Scopus subject areas

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