The blood–tumour barrier in cancer biology and therapy

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.