Anticancer therapies and CNS relapse: overcoming blood-brain and blood-cerebrospinal fluid barrier impermeability.
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.
Chamberlain
Marc C
MC
Department of Neurology and Neurological Surgery, University of Washington, Fred Hutchinson Cancer Center, Seattle, WA 98109-1023, USA. chambemc@u.washington.edu
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001812:Blood-Brain Barrier / Q000502:physiology*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D003131:Combined Modality Therapy; D006801:Humans; D007278:Injections, Spinal; D009362:Neoplasm Metastasis / Q000188:drug therapy; D019635:Neurosurgical Procedures; D011878:Radiotherapy
D000970:Antineoplastic Agents