Is the blood-brain barrier really disrupted in all glioblastomas? A critical assessment of existing clinical data

Jann N. Sarkaria, Leland S. Hu, Ian F. Parney, Deanna H. Pafundi, Debra H. Brinkmann, Nadia N. Laack, Caterina Giannini, Terence C. Burns, Sani H. Kizilbash, Janice K. Laramy, Kristin R. Swanson, Timothy J. Kaufmann, Paul D. Brown, Nathalie Y.R. Agar, Evanthia Galanis, Jan C. Buckner, William F. Elmquist

Research output: Contribution to journalArticlepeer-review

100 Scopus citations

Abstract

The blood-brain barrier (BBB) excludes the vast majority of cancer therapeutics from normal brain. However, the importance of the BBB in limiting drug delivery and efficacy is controversial in high-grade brain tumors, such as glioblastoma (GBM). The accumulation of normally brain impenetrant radiographic contrast material in essentially all GBM has popularized a belief that the BBB is uniformly disrupted in all GBM patients so that consideration of drug distribution across the BBB is not relevant in designing therapies for GBM. However, contrary to this view, overwhelming clinical evidence demonstrates that there is also a clinically significant tumor burden with an intact BBB in all GBM, and there is little doubt that drugs with poor BBB permeability do not provide therapeutically effective drug exposures to this fraction of tumor cells. This review provides an overview of the clinical literature to support a central hypothesis: that all GBM patients have tumor regions with an intact BBB, and cure for GBM will only be possible if these regions of tumor are adequately treated.

Original languageEnglish (US)
Pages (from-to)184-191
Number of pages8
JournalNeuro-Oncology
Volume20
Issue number2
DOIs
StatePublished - Jan 22 2018

Bibliographical note

Funding Information:
This work was supported by the MIT/Mayo Physical Sciences Center for Drug Distribution and Efficacy in Brain Tumors (U54CA210180), the Mayo Clinic SPORE in Brain Cancer (P50CA108961), and RO1NS077921. We gratefully acknowledge the support of the MIT/Mayo Physical Sciences Center for Drug Distribution and Efficacy in Brain Tumors (U54CA210180), the James S. McDonnell Foundation, the Ivy Foundation, the Mayo Clinic SPORE in Brain Cancer (P50CA108961) and the NIH (RO1NS077921, R01 NS060752, R01 CA164371, U54 CA210180, U54 CA143970, U54 CA193489, U01CA220378).

Publisher Copyright:
© The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved.

Keywords

  • blood brain barrier
  • drug therapy
  • glioblastoma
  • magnetic resonance imaging

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