Human epidermal growth factor receptor 2

Wolff AC, Hammond MEH, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer. Arch. Pathol. Lab. Med. 2007 131 18-43. 

Figure 7.3 The ER 1D5 peptide only binds to the ER 1D5 mAb (upper left and lower right). Other mAbs do not bind. The antibody abbreviations in the lower panel are Her2 11G5, and 9C2, human epidermal growth factor receptor type 2 clones 11G5 and 9C2 Mela-HMB45, melanocyte-specific antibody clone HMB45 Vimen V9, vimentin clone V9 Anti-LCA, anti-leukocyte common antigen clones PD7/26 and 2B11, combined as a cocktail Mouse poly IgG, mouse polyclonal IgG. Reproduced with permission from Sompuram et al.7...

Wolff A, Hammond M, Schwartz J, et al. American Society of Clinical Oncology/ College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J. Clin. Oncol. 2007 25 118-145. 

Note IL2, interluekin 2 HER2, human epidermal growth factor receptor 2 RSV, respiratory syncytial virus TNF, tumor necrosis factor IgE, Immunoglobulin E EGER, epidermal growth factor receptor VEGF, vascular endothelial growth factor. 

Trastuzumab is licensed for the treatment of early breast cancer that overexpresses human epidermal growth factor receptor-2 (HER2). It may be administered as monotherapy or in combination with, for example, paclitaxel, docetaxel (taxanes) or anastrozole (aromatase inhibitors). Since trastuzumab can cause cardiotoxicity, concomitant use with anthracyclines such as... 

HER2 human epidermal growth factor receptor-2... 

Herceptin (Trastuzumab, humanized antibody directed against HER2, i.e. human epidermal growth factor receptor 2)... 

GotohN, Tojo A, Hino M et al. A highly conserved tyrosine residue at codon 845 within the kinase domain is not required for the transforming activity of human epidermal growth factor receptor. Biochem... 

Wissner A, Overbeek E, Reich MF et al. Synthesis and structure-activity relationships of 6,7-disubstituted 4-anilinoquinoline-3-carbonitriles. The design of an orally active, irreversible inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) and the human epidermal growth factor receptor-2 (ElER-2). JMed Chem 2003 46 49-63. 

Trastuzumab is a recombinant DNA-derived, humanized monoclonal antibody that binds to the extracellular domain of the human epidermal growth factor receptor HER-2/ . This antibody blocks the natural ligand from binding and down-regulates the receptor. Trastuzumab is approved for the treatment of metastatic breast cancer in patients whose tumors overexpress HER-2/ . As a single agent it induces remission in about 15-20% of patients in combination with chemotherapy, it increases response rate and duration as well as 1-year survival. Trastuzumab is under investigation for other tumors that express HER-2... 

Van de Vijver, M. J. 2001. Assessment of the need and appropriate method for testing for the human epidermal growth factor receptor-2 (HER2). Eur. J. Cancer 37 511-517. 

Bevacizumab, a humanized IgG and cetuximab, a chimeric IgGx, are currently marketed in the US for treatment of metastatic colorectal cancer [92, 93]. Bevacizumab neutralizes the biological activity of vascular endothelial growth factor (VEGF), while cetuximab binds specifically to the extracellular domain of the human epidermal growth factor receptor (EGFR). Bevacizumab, in combination with IV 5-fluorouracil (5-FU) -based chemotherapy, is indicated for first-line treatment of metastatic colorectal cancer, whereas cetuximab is used in patients refractory to or intolerant to irinotecan-based chemotherapy. The clinical pharmacokinetics of cetuximab are discussed in detail in Chapter 14. 

Fendly, B. M., Winget, M., Hudziak, R. M., Lipari, M. T., Napier, M. A., and Ullrich, A. (1990). Characterization of murine monoclonal antibodies reactive to either the human epidermal growth factor receptor or HER2/neu gene product. Cancer Res. 50,1550-1558. 

Zhang DH, Tai LK, Wong LL, Sethi SK, Koay ES. Proteomics of breast cancer Enhanced expression of cytokeratinl9 in human epidermal growth factor receptor type 2 positive breast tumors. Proteomics 2005 5(7) 1797-1805. 

Twenty-seven out of 44 FDA-approved biopharmaceuticals have been tested in a battery of genotoxicity assays. Eighty-five different assays performed yielded negative results. The most commonly performed assays were the Ames test, the chromosomal aberration assay in human lymphocytes, the mouse lymphoma gene mutation assay, and the mammalian in vivo erythrocyte micronucleus test. Examples of the range of biopharmaceutical products tested include, domase alfa (deoxyribonuclease I-DNAse), trastuzumab (mAb to human epidermal growth factor receptor 2), alteplase (tissue plasminogen activator), infliximab (mAb to the human tumor necrosis factor a). 

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