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The Human Epidermal Growth Factor Receptor (HER) Family: Structure and Function

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Guide to Targeted Therapies: EGFR mutations in NSCLC

Abstract

Epidermal growth factor receptor (EGFR) belongs to a family of four different receptors, including EGFR (ErbB-1; human epidermal growth factor receptor 1 [HER1]), HER2 (c-ErbB-2), HER3 (c-ErbB-3), and HER4 (c-ErbB-4). These proteins are coded by distinct genes that are expressed on chromosomes 7, 17, 12, and 2, respectively. Although specific soluble ligands have been identified for the extracellular domains of EGFR, HER3, and HER4, no ligand has been identified for HER2.

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References

  1. Lewis TS, Shapiro PS, Ahn NG. Signal transduction through MAP kinase cascades. Adv Cancer Res. 1998;74:49-139.

    Google Scholar 

  2. Cohen BD, Kiener PA, Green JM, et al. The relationship between human epidermal growthlike factor receptor expression and cellular transformation in NIH3T3 cells. J Biol Chem. 1996;271:30897-30903.

    Google Scholar 

  3. Grandis JR, Sok JC. Signaling through the epidermal growth factor receptor during the development of malignancy. Pharmacol Ther. 2004;102:37-46.

    Google Scholar 

  4. Salomon DS, Brandt R, Ciardiello F, et al. Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol. 1995;19:183-232.

    Google Scholar 

  5. Normanno N, Bianco C, Strizzi L, et al. The ErbB receptors and their ligands in cancer: an overview. Curr Drug Targets. 2005;6:243-257.

    Google Scholar 

  6. Pinkas-Kramarski R, Soussan L, Waterman H, et al. Diversification of Neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions. EMBO J. 1996;15:2452-2467.

    Google Scholar 

  7. Nicholson RI, Gee JM, Harper ME, et al. EGFR and cancer prognosis. Eur J Cancer. 2001;37 (Suppl 4):S9-S15.

    Google Scholar 

  8. Meert AP, Martin B, Delmotte P, et al. The role of EGF-R expression on patient survival in lung cancer: a systematic review with meta-analysis. Eur Respir J. 2002;20:975-981.

    Google Scholar 

  9. Bailey LR, Kris M, Wolf M, et al. Tumor EGFR membrane staining is not clinically relevant for predicting response in patients receiving gefitinib (‘Iressa’, ZD1839) monotherapy for pretreated advanced non-small-cell lung cancer: IDEAL 1 and 2. Clin Cancer Res. 2003;44:1362, LBA-170.

    Google Scholar 

  10. Cappuzzo F, Gregorc V, Rossi E, et al. Gefitinib in pretreated non-small-cell lung cancer (NSCLC): analysis of efficacy and correlation with HER2 and epidermal growth factor receptor expression in locally advanced or metastatic NSCLC. J Clin Oncol. 2003;21:2658-2663.

    Google Scholar 

  11. Tsao MS, Sakurada A, Cutz JC, et al. Erlotinib in lung cancer molecular and clinical predictors of outcome. N Engl J Med. 2005;353:133-144.

    Google Scholar 

  12. Hirsch Fr, Varella-Garcia M, Bunn Pa Jr, et al. Molecular predictors of outcome with gefitinib in a phase III placebo-controlled study in advanced non-small-cell lung cancer. J Clin Oncol. 2006;24:5034-5042.

    Google Scholar 

  13. Cappuzzo F, Ciuleanu T, Stelmakh L, et al. Erlotinib as maintenance treatment in advanced non-small-cell lung cancer: a multicentre, randomised, placebo-controlled phase 3 study. Lancet Oncol. 2010;11:521-529.

    Google Scholar 

  14. Mazieres J, Brugger W, Cappuzzo F, et al. Evaluation of EGFR protein expression by immunohistochemistry using H-score and the magnification rule: re-analysis of the SATURN study. Lung Cancer. 2013;82:231-237.

    Google Scholar 

  15. Zhang X, Pickin KA, Bose R, et al. Inhibition of the EGF receptor by binding of MIG6 to an activating kinase domain interface. Nature. 2007;450:741-744.

    Google Scholar 

  16. Chang X, Izumchenko E, Solis LM, et al. The relative expression of Mig6 and EGFR is associated with resistance to EGFR kinase inhibitors. PLoS One. 2013;8:e68966.

    Google Scholar 

  17. Cappuzzo F, Hirsch FR, Rossi E, et al. Epidermal growth factor receptor gene and protein and gefitinib sensitivity in non-small-cell lung cancer. J Natl Cancer Inst. 2005;97:643-655.

    Google Scholar 

  18. Cappuzzo F, Marchetti A, Skokan M, et al. Increased MET gene copy number negatively affects survival of surgically resected non-small-cell lung cancer patients. J Clin Oncol. 2009;27:1667-1674.

    Google Scholar 

  19. Hirsch FR, Varella-Garcia M, Bunn PA Jr, et al. Epidermal growth factor receptor in non-smallcell lung carcinomas: correlation between gene copy number and protein expression and impact on prognosis. J Clin Oncol. 2003;21:3798-3807.

    Google Scholar 

  20. Jeon YK, Sung SW, Chung JH, et al. Clinicopathologic features and prognostic implications of epidermal growth factor receptor (EGFR) gene copy number and protein expression in nonsmall cell lung cancer. Lung Cancer. 2006;54:387-398.

    Google Scholar 

  21. Suzuki S, Dobashi Y, Sakurai H, et al. Protein overexpression and gene amplification of epidermal growth factor receptor in non small cell lung carcinomas. An immunohistochemical and fluorescence in situ hybridization study. Cancer. 2005;103:1265-1273.

    Google Scholar 

  22. Cappuzzo F, Skokan M, Gajapathy S, et al. Effect of increased MET gene copy number on survival of surgically resected non-small cell lung cancer (NSCLC) patients. Data presented at the 2008 ASCO Annual Meeting; May 30-June 1, 2008. Abstract 11047.

    Google Scholar 

  23. Shepherd F, Ding K, Sakurada A, et al. Updated molecular analyses of exons 19 and 21 of the epidermal growth factor receptor (EGFR) gene and codons 12 and 13 of the KRAS gene in non-small cell lung cancer (NSCLC) patients treated with erlotinib in National Cancer Institute of Cancer. J Clin Oncol. 2007;25:7571a.

    Google Scholar 

  24. Cappuzzo F, Ligorio C, Janne PA, et al. Prospective study of gefitinib in epidermal growth factor receptor fluorescence in situ hybridization-positive/phospho-Akt-positive or never smoker patients with advanced non-small-cell lung cancer: the ONCOBELL trial. J Clin Oncol. 2007;25:2248-2255.

    Google Scholar 

  25. Fukuoka M, Wu YL, Thongprasert S, et al. Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS). J Clin Oncol. 2011;29:2866-2874.

    Google Scholar 

  26. Brugger W, Triller N, Blasinska-Morawiec M, et al. Prospective molecular marker analyses of EGFR and KRAS from a randomized, placebo-controlled study of erlotinib maintenance therapy in advanced non-small-cell lung cancer. J Clin Oncol. 2011;29:4113-4120.

    Google Scholar 

  27. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N Engl J Med. 2009;361:947-957.

    Google Scholar 

  28. Lynch TJ, Bell DW, Sordella R et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med. 2004;350:2129-2139.

    Google Scholar 

  29. Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer: Correlation with clinical response to gefitinib therapy. Science. 2004;304:1497-1500.

    Google Scholar 

  30. Pao W, Miller V, Zakowski M, et al. EGF receptor gene mutations are common in lung cancers from “never smokers” and are associated with sensitivity of tumors to gefitinib and erlotinib. PNAS USA. 2004;101:13306-13311.

    Google Scholar 

  31. Pham D, Kris MG, Riely GJ, et al. Use of cigarette-smoking history to estimate the likelihood of mutations in epidermal growth factor receptor gene exons 19 and 21 in lung adenocarcinomas. J Clin Oncol. 2006;24:1700-1704.

    Google Scholar 

  32. Marchetti A, Felicioni L, Buttitta F, et al. Assessing EGFR mutations. N Engl J Med. 2006;354:526-528.

    Google Scholar 

  33. Yasuda H, Kobayashi S, Costa DB, et al; EGFR exon 20 insertion mutations in non-small-cell lung cancer: preclinical data and clinical implications. Lancet Oncol. 2012;13:e23-e31.

    Google Scholar 

  34. Riely GJ, Pao W, Pham D, et al. Clinical course of patients with non-small cell lung cancer and epidermal growth factor receptor exon 19 and exon 21 mutations treated with gefitinib or erlotinib. Clin Cancer Res. 2006;12:839-844.

    Google Scholar 

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Authors and Affiliations

  1. Medical Oncology Department, Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy

    Federico Cappuzzo

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  1. Federico Cappuzzo
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© 2014 Springer International Publishing Switzerland

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Cappuzzo, F. (2014). The Human Epidermal Growth Factor Receptor (HER) Family: Structure and Function. In: Guide to Targeted Therapies: EGFR mutations in NSCLC. Adis, Cham. https://doi.org/10.1007/978-3-319-03059-3_2

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  • DOI: https://doi.org/10.1007/978-3-319-03059-3_2

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  • Publisher Name: Adis, Cham

  • Print ISBN: 978-3-319-03058-6

  • Online ISBN: 978-3-319-03059-3

  • eBook Packages: MedicineMedicine (R0)

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