Anticancer therapies and CNS relapse: overcoming blood––brain and blood––cerebrospinal fluid barrier impermeability. (April 2010)

• Record Type: Journal Article
• Authors: Chamberlain, Marc C
• Is Part Of: Expert review of neurotherapeutics. Volume 10:Number 4(2010)
• Page Start: 547
• Page End: 561
• Publication Date: 2010-04
• Subjects: BBB -- blood––cerebrospinal fluid barrier -- central nervous system -- cerebrospinal fluid -- CNS -- intra-cerebrospinal fluid -- leptomeningeal -- targeted therapies; Neuropharmacology -- Periodicals; 615.7805
• DOI: 10.1586/ern.10.14
• Languages: English
• ISSNs: 1473-7175

Abstract

Prolonged survival with targeted therapies has sometimes come at the expense of an increased risk of CNS relapse; because many of these agents poorly penetrate the BBB, malignant cells may remain viable within the CNS. The ability of anticancer drugs to penetrate the BBB is a major consideration in the treatment of CNS parenchymal metastases. Optimal chemotherapy approaches for treating CNS metastases remain unclear due to a lack of evidence-based recommendations. Recent hypothesis-generating studies evaluating intra-cerebrospinal fluid administration of targeted agents indicate that these drugs may be effective in treating leptomeningeal disease and are associated with a low incidence of drug-related adverse events. Newer strategies for treating cerebrospinal fluid metastases may co-opt endogenous systems of the BBB, such as those involved in receptor-mediated transcytosis or classic carrier-mediated transporter systems to facilitate drug delivery across the BBB.