Anticancer therapies and CNS relapse: overcoming blood–brain and blood–cerebrospinal fluid barrier impermeability

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.

Keywords::

• BBB
• blood–cerebrospinal fluid barrier
• central nervous system
• cerebrospinal fluid
• CNS
• intra-cerebrospinal fluid
• leptomeningeal
• targeted therapies

Financial & competing interests disclosure

Editorial support was provided by Ann Yeung (Phase Five Communications Inc., NY, USA) with financial support from Enzon Pharmaceuticals, Inc. (NJ, USA). The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No other writing assistance was utilized in the production of this manuscript.