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ErbB receptors: from oncogenes to targeted cancer therapies
Hongtao Zhang, … , Ramachandran Murali, Mark I. Greene
Hongtao Zhang, … , Ramachandran Murali, Mark I. Greene
Published August 1, 2007
Citation Information: J Clin Invest. 2007;117(8):2051-2058. https://doi.org/10.1172/JCI32278.
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Review

ErbB receptors: from oncogenes to targeted cancer therapies

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Abstract

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.

Authors

Hongtao Zhang, Alan Berezov, Qiang Wang, Geng Zhang, Jeffrey Drebin, Ramachandran Murali, Mark I. Greene

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Figure 2

Molecules in the ErbB signaling pathways as targets for cancer therapies.

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Molecules in the ErbB signaling pathways as targets for cancer therapies...
FDA-approved drugs include three mAbs targeting the extracellular domain of ErbB and three TKIs targeting the kinase domains. Trastuzumab targets p185her2/neu. Cetuximab and panitumumab target EGFR. Some TKIs (gefitinib, erlotinib) are only specific for EGFR, while lapatinib and HKI-272 also broadly inhibit other receptors in the family. Inhibitors to molecules downstream of ErbB signaling pathways, such as Src, AKT, survivin, and mTor, are also potential therapeutics for ErbB-mediated transformation. AHNP-SA, AHNP-streptavidin; scFv, single-chain variable fragment.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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