1. Nat. Rev. Clin. Oncol. doi:10.1038/nrclinonc.2017.95
Figure 1 Effect of administration routes on uptake of antibody–drug therapies and other drugs
Figure 1 | Effect of administration routes on uptake of antibody–drug therapies and other drugs. a | In non-malignant brain tissue, or in the presence of microscopic tumour foci, the intact blood brain barrier (BBB) is a physical barrier that efficiently prevents egress of systemically administered drugs and monoclonal antibodies from the bloodstream into the brain parenchyma, as a result of the presence of tight junctions between the endothelial cells, and the presence of surrounding non-neoplastic cellular structures, such as pericytes and astrocytic foot processes. b | In high-grade gliomas, relative disruption of the BBB occurs, indicated by the presence of contrast-agent extravasation detected on radiological imaging. Limited amounts of drugs are able to egress from the systemic circulation into the tumour. Some of these therapeutic agents are then removed via efflux pumps (protein transporters), such as P-glycoprotein or multidrug resistance protein on tumour cells. c | Convection-enhanced delivery (CED) is a strategy for enhancing drug delivery by infusing drugs under positive pressure through intracerebral placement of catheters. Advantages of the CED approach include bypass of the BBB, limited systemic accumulation of the drug and associated toxicity, and improved volume of intracranial distribution (owing to the drug being pumped throughout the brain interstitium). Factors that can negatively affect the efficacy of the CED approach include the need for surgical expertise in catheter placement, the possibility of infused drug not reaching all areas of the tumour, and catheter-related complications34,40,41,44.
Gan, H. K. et al. (2017) Antibody–drug conjugates in glioblastoma therapy: the right drugs to the right cells
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