Human epidermal growth factor receptor HER

Wissner A, Overbeek E, Reich MF et al (2003) 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 (HER-2). J Med Chem 46 49-63... 

Howe, L.R. et al., Celecoxib, a selective cyclooxygenase 2 inhibitor, protects against human epidermal growth factor receptor 2 (HER-2)/neu-induced breast cancer. Cancer Res., 62 (19),... 

Human epidermal growth factor receptor-2 (HER-2 neu) is a member of the type 1 receptor tyrosine kinase family with domains on the cell surface, functioning as growth factor receptors. The type 1 receptor tyrosine kinase family includes the receptors HER-1 (EGFRorc-erbBl), HER-2 (c-erbB-2), HER-3 (c-erbB-3) and HER-4 (c-erbB-4). 

Figure 25 Amphiphiiic copoiymer for tumor targeting and drug delivery. Antibodies targeted to the human epidermal growth factor receptor-2 (HER-2) on cancer cells were appended to the polymer through conjugation of exposed lysine residues. The conjugates are taken up in cancer cells. Ts, tosyl.

First-line chemotherapy for the treatment of metastatic breast cancer is now largely dependent on the patient s HER-2 antigen status. The HER-2 (human epidermal growth factor receptor 2) protein is overexpressed on the surface of breast cancer cells in approximately 15-25% of patients. The measurement of this protein can be performed by immunohistochemistry methods, where the degree of protein expression is denoted by negative, 1+, 2+ or 3+. As Mrs CR s has HER-2,3+ disease, this denotes strong protein overexpression. 

First-line treatment of her metastatic breast cancer should therefore incorporate the monoclonal antibody trastuzumab (Herceptin). NICE (2002b) have issued a technology appraisal on the use of trastuzumab in metastatic breast cancer which states that trastuzumab be used in combination with paclitaxel for women with tumours with excessive human epidermal growth factor receptor 2 (HER2) at levels of 3+ who have not had chemotherapy for metastatic breast cancer and for whom anthracycline treatment is inappropriate. ... 

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... 

Erlotinib is an epidermal growth factor receptor inhibitor that inhibits intracellular phosphorylation of tyrosine kinase associated with the epidermal growth factor receptor. It is indicated in the treatment of locally advanced or metastatic non-small-cell lung cancer after failure of at least 1 prior chemotherapy regimen. Erlotinib (Tarceva) is a human HER 1/EGER tyrosine kinase inhibitor with the following chemical formula A-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine. It is indicated in treatment of patients with locally advanced or metastatic non-small-cell lung cancer. 

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