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

Expert Rev Neurother. 2010 Apr;10(4):547-61. doi: 10.1586/ern.10.14.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Blood-Brain Barrier / physiology*
  • Central Nervous System Neoplasms / drug therapy*
  • Central Nervous System Neoplasms / radiotherapy
  • Central Nervous System Neoplasms / surgery
  • Combined Modality Therapy
  • Humans
  • Injections, Spinal
  • Neoplasm Metastasis / drug therapy
  • Neurosurgical Procedures
  • Radiotherapy


  • Antineoplastic Agents