Blood–Brain Barrier in Brain Tumors: Biology and Clinical Relevance

Abstract

The presence of barriers, such as the blood–brain barrier (BBB) and brain–tumor barrier (BTB), limits the penetration of antineoplastic drugs into the brain, resulting in poor response to treatments. Many techniques have been developed to overcome the presence of these barriers, including direct injections of substances by intranasal or intrathecal routes, chemical modification of drugs or constituents of BBB, inhibition of efflux pumps, physical disruption of BBB by radiofrequency electromagnetic radiation (EMP), laser-induced thermal therapy (LITT), focused ultrasounds (FUS) combined with microbubbles and convection enhanced delivery (CED). However, most of these strategies have been tested only in preclinical models or in phase 1–2 trials, and none of them have been approved for treatment of brain tumors yet. Concerning the treatment of brain metastases, many molecules have been developed in the last years with a better penetration across BBB (new generation tyrosine kinase inhibitors like osimertinib for non-small-cell lung carcinoma and neratinib/tucatinib for breast cancer), resulting in better progression-free survival and overall survival compared to older molecules. Promising studies concerning neural stem cells, CAR-T (chimeric antigen receptors) strategies and immunotherapy with checkpoint inhibitors are ongoing.

EGFR mutation prevalence, real-world treatment patterns, and outcomes among patients with resected, early-stage, non-small cell lung cancer in Canada

“…Further, as noted above, the CNS was the fourth most common site of distant metastasis. As some chemotherapies do not penetrate the blood-brain [36], patients who receive these agents in the adjuvant setting remain at risk for CNS metastases, which are associated with a poor prognosis. Effective adjuvant therapies that penetrate the CNS are needed.…”

Brain Cancer Chemotherapy through a Delivery System across the Blood-Brain Barrier into the Brain Based on Receptor-Mediated Transcytosis Using Monoclonal Antibody Conjugates

“…VEGFs secreted from brain cancer cells induced angiogenesis, lost the astrocyte endfeet, and destroyed the tight junctions to form fenestration (up to 15 nm in diameter between common endothelial cells, potentially including the BBB [ 36 , 37 ]). Even such a BBB scenario, called the brain–tumor barrier, restricted material permeation to some extent, which permeation was conducted through the paracellular fenestration pathway and transcellular pinocytosis [ 38 , 39 ]. It seems likely that brain cancers substantially occupy the endothelial cells while alive, some of which are established by VEGF-induced angiogenesis, to deliver themselves nutrients.…”

Adoptive Cell Therapy in Pediatric and Young Adult Solid Tumors: Current Status and Future Directions

“…Trafficking can be inhibited by physical barriers, loss of MHC class 1 expression, repellent cytokine gradients, expression of inhibitory ligands such as PD-L1, and abnormal tumor vasculature ( 82 ). CNS tumors are further shielded by the blood-brain barrier ( 83 ). If ACTs cannot traffic to the tumor and engage their target antigen, they fail to be activated and expand, leading to rapid loss of ACT.…”