The protective blood–brain barrier has a major role in ensuring normal brain function by severely limiting and tightly controlling the ingress of substances into the brain from the circulation. In primary brain tumours, such as glioblastomas, as well as in brain metastases from cancers in other organs, including lung and breast cancers and melanoma, the blood–brain barrier is modified and is referred to as the blood–tumour barrier (BTB). Alterations in the BTB affect its permeability, and this structure participates in reciprocal regulatory pathways with tumour cells. Importantly, the BTB typically retains a heterogeneous capacity to restrict the penetration of many therapeutic agents into intracranial tumours, and overcoming this challenge is a key to improving the effectiveness of treatment and patient quality of life. Herein, current knowledge of BTB structure and function is reviewed from a cell and cancer biology standpoint, with a focus on findings derived from in vivo models and human tumour specimens. Additionally, how this knowledge can be translated into clinical advances for patients with cancer is discussed.
The blood–brain barrier surrounding capillaries in the brain parenchyma is modified to a blood–tumour barrier (BTB) upon the development of primary or metastatic brain tumours.
The BTB is heterogeneously permeable to many drugs, contributing to poor therapeutic efficacy.
Research has uncovered consistent changes in BTBs. BTB permeability has been changed by modifying select alterations, indicating that the BTB presents viable molecular targets for improving drug efficacy.
New brain-penetrant molecularly targeted inhibitors of oncoproteins have demonstrated efficacy in subgroups of patients with brain metastasis.
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The author thanks M. Gilbert, A. Zimmer, W. D. Figg, B. Gril, I. Khan and S. Lipkowitz for critical review of the manuscript.
The author declares no competing interests.
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Nature Reviews Clinical Oncology thanks Twan Lammers, Seyed Alireza Mansouri, Timothy Phoenix and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Steeg, P.S. The blood–tumour barrier in cancer biology and therapy. Nat Rev Clin Oncol 18, 696–714 (2021). https://doi.org/10.1038/s41571-021-00529-6
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