ErbB receptors: from oncogenes to targeted cancer therapies

• Published in: The Journal of clinical investigation Vol. 117; no. 8; pp. 2051 - 2058
• Main Authors: Zhang, Hongtao, Berezov, Alan, Wang, Qiang, Zhang, Geng, Drebin, Jeffrey, Murali, Ramachandran, Greene, Mark I
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01.08.2007
• Subjects: Animals; Antibodies, Monoclonal - therapeutic use; Biomedical research; Cancer; Care and treatment; Cytotoxicity; Drug Delivery Systems; Enzyme Activation - drug effects; Enzyme Inhibitors - therapeutic use; ErbB Receptors - antagonists & inhibitors; ErbB Receptors - genetics; ErbB Receptors - metabolism; Gene amplification; Genetic aspects; Growth factors; Humans; Kinases; Leukemia; Ligands; Lymphatic system; Medical prognosis; Molecular weight; Mutation; Neoplasms - drug therapy; Neoplasms - enzymology; Neoplasms - genetics; Oncogenes; Protein Structure, Tertiary; Proteins; Receptor antibodies; Review Series; Signal transduction; Tumors; United States
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/jci32278

Understanding the genetic origin of cancer at the molecular level has facilitated the development of novel targeted therapies. Aberrant activation of the ErbB family of receptors is implicated in many human cancers and is already the target of several anticancer therapeutics. The use of mAbs specific for the extracellular domain of ErbB receptors was the first implementation of rational targeted therapy. The cytoplasmic tyrosine kinase domain is also a preferred target for small compounds that inhibit the kinase activity of these receptors. However, current therapy has not yet been optimized, allowing for opportunities for optimization of the next generation of targeted therapy, particularly with regards to inhibiting heteromeric ErbB family receptor complexes.