Revoking the privilege: targeting HER2 in the central nervous system.
Pharmacologic agents developed for cancer therapy have traditionally relied on a therapeutic ratio of effects between tumors and normal tissue. Over the past decade, this concept has been refined through the development of agents that are intended to specifically target tumor cells. The epidermal growth factor receptor (EGFR) (ErbB) family of receptor tyrosine kinases is an intensely studied target in many cancer cell types, and several successful therapeutic agents have been developed to block the growth promoting functions of these receptors. However, with their success has come the evolution of novel clinical scenarios by which tumor cells can evade these targeted therapies. Trastuzumab, a monoclonal antibody to Her2/ErbB2 that is used in breast cancer, has been shown to provide a survival benefit for patients whose tumors express this receptor but it does not have activity in the central nervous system because of the blood-brain barrier. In this issue of Molecular Pharmacology, Emanuel et al. (p. 328) report on a tyrosine kinase inhibitor that targets Her2/neu and also crosses the blood-brain barrier. Efforts to improve current strategies of targeting this receptor may lead not only to benefits in the treatment of breast cancer but also to advances in the treatment of other central nervous system malignancies, such as gliomas and medulloblastoma.
Contessa
Joseph N
JN
The Department of Radiation Oncology, The University of Michigan Medical Center, UH B2 C490, Box 0010, Ann Arbor, MI 48109-0010, USA. jcontess@med.umich.edu
Hamstra
Daniel A
DA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D002490:Central Nervous System / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods; D018390:Gene Targeting / Q000379:methods; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D018719:Erb-b2 Receptor Tyrosine Kinases