表皮生长因子受体

表皮生长因子受体（英語：epidermal growth factor receptor，简称为EGFR、ErbB-1或HER1）是一类名为表皮生长因子家族（EGF-家族）的细胞外蛋白配体的细胞表面受体 。 表皮生长因子受体是ErbB受体家族家族的成员之一，ErbB家族是包含四种紧密联系蛋白的亚家族，这四种蛋白分别是受体酪氨酸激酶类：EGFR（ErbB-1）、HER2/c-neu（ErbB-2）、Her 3（ErbB-3）以及Her 4（ErbB-4）。影响EGFR表达或活性的突变可能导致癌症。 表皮生长因子及其受体是由范德堡大学的斯坦利·科恩发现的，科恩与丽塔·列维-蒙塔尔奇尼因发现生长因子类而共同获得了1986年诺贝尔生理学或医学奖。 表皮生长因子受体（EGFR）存在于细胞表面且因结合特异性受体而被活化，这些受体包括表皮生长因子和转化生长因子-α。ErbB2并无已知的直接活化配体，可能结构性地处于活化状态，或在与如EGFR等其他家族成员形成异源二聚体时被活化。 除了參與正常的生理功能之外，EGFR在癌症中同樣扮演了重要的角色，以非小細胞性肺癌(NSCLC)為例，在全球患有非小細胞性肺癌的病患中，高達20%都表現了EGFR基因的突變，所以目前的藥物多朝向EGFR tyrosine kinase inhibitor去做設計，以期達到治療的效果。 目前發現具有EGFR突變型的NSCLC癌細胞會對tyrosine kinase inhibitor產生抗藥作用，這個抗藥作用可能來自於其中細胞大量的endothelin表現，進而使腫瘤組織血管收縮，降低了抗癌藥物的灌流，產生類似抗藥性的效果。 Kathryn M. Ferguson, Mitchell B. Berger, Jeannine M. Mendrola, Hyun Soo Cho, Daniel J. Leahy, Mark A. Lemmon. EGF activates its receptor by removing interactions that autoinhibit ectodomain dimerization. Molecular Cell. 2003-02, 11 (2): 507–517 [2019-05-26]. ISSN 1097-2765. PMID 12620237.  Herbst RS. Review of epidermal growth factor receptor biology. Int. J. Radiat. Oncol. Biol. Phys. 2004, 59 (2 Suppl): 21–6. PMID 15142631. doi:10.1016/j.ijrobp.2003.11.041.  Zhang H, Berezov A, Wang Q, Zhang G, Drebin J, Murali R, Greene MI. ErbB receptors: from oncogenes to targeted cancer therapies. J. Clin. Invest. August 2007, 117 (8): 2051–8. PMC 1934579 . PMID 17671639. doi:10.1172/JCI32278.  Yuhong Lu , Yanfeng Liu , Sebastian Oeck , Gary J. Zhang , Alexander Schramm , and Peter M. Glazer. Hypoxia Induces Resistance to EGFR Inhibitors in Lung Cancer Cells via Upregulation of FGFR1 and the MAPK Pathway. Cancer Res. 2020-11-01, 80 (21): 4655-4667. doi:10.1158/0008-5472.CAN-20-1192.  A.A. Armour, C.L. Watkins. The challenge of targeting EGFR: experience with gefitinib in non small cell lung cancer. Cancer Res. 2020-10-01, 80 (19): 4023-4024. doi:10.1158/0008-5472.CAN-20-0141.  Carpenter G. Receptors for epidermal growth factor and other polypeptide mitogens. Annu. Rev. Biochem. 1987, 56 (1): 881–914. PMID 3039909. doi:10.1146/annurev.bi.56.070187.004313.  Boonstra J, Rijken P, Humbel B; et al. The epidermal growth factor. Cell Biol. Int. 1995, 19 (5): 413–30. PMID 7640657. doi:10.1006/cbir.1995.1086.  引文格式1维护：显式使用等标签 (link) Carpenter G. The EGF receptor: a nexus for trafficking and signaling. BioEssays. 2000, 22 (8): 697–707. PMID 10918300. doi:10.1002/1521-1878(200008)22:8<697::AID-BIES3>3.0.CO;2-1.  Filardo EJ. Epidermal growth factor receptor (EGFR) transactivation by estrogen via the G-protein-coupled receptor, GPR30: a novel signaling pathway with potential significance for breast cancer. J. Steroid Biochem. Mol. Biol. 2002, 80 (2): 231–8. PMID 11897506. doi:10.1016/S0960-0760(01)00190-X.  Tiganis T. Protein tyrosine phosphatases: dephosphorylating the epidermal growth factor receptor. IUBMB Life. 2002, 53 (1): 3–14. PMID 12018405. doi:10.1080/15216540210811.  Di Fiore PP, Scita G. Eps8 in the midst of GTPases. Int. J. Biochem. Cell Biol. 2002, 34 (10): 1178–83. PMID 12127568. doi:10.1016/S1357-2725(02)00064-X.  Benaim G, Villalobo A. Phosphorylation of calmodulin. Functional implications. Eur. J. Biochem. 2002, 269 (15): 3619–31. PMID 12153558. doi:10.1046/j.1432-1033.2002.03038.x.  Leu TH, Maa MC. Functional implication of the interaction between EGF receptor and c-Src. Front. Biosci. 2004, 8 (1-3): s28–38. PMID 12456372. doi:10.2741/980.  Anderson NL, Anderson NG. The human plasma proteome: history, character, and diagnostic prospects. Mol. Cell Proteomics. 2003, 1 (11): 845–67. PMID 12488461. doi:10.1074/mcp.R200007-MCP200.  Kari C, Chan TO, Rocha de Quadros M, Rodeck U. Targeting the epidermal growth factor receptor in cancer: apoptosis takes center stage. Cancer Res. 2003, 63 (1): 1–5. PMID 12517767.  Bonaccorsi L, Muratori M, Carloni V; et al. Androgen receptor and prostate cancer invasion. Int. J. Androl. 2003, 26 (1): 21–5. PMID 12534934. doi:10.1046/j.1365-2605.2003.00375.x.  引文格式1维护：显式使用等标签 (link) Reiter JL, Maihle NJ. Characterization and expression of novel 60-kDa and 110-kDa EGFR isoforms in human placenta. Annals of the New York Academy of Sciences. 2003, 995 (1): 39–47. PMID 12814937. doi:10.1111/j.1749-6632.2003.tb03208.x.  Adams TE, McKern NM, Ward CW. Signalling by the type 1 insulin-like growth factor receptor: interplay with the epidermal growth factor receptor. Growth Factors. 2005, 22 (2): 89–95. PMID 15253384. doi:10.1080/08977190410001700998.  Ferguson KM. Active and inactive conformations of the epidermal growth factor receptor. Biochem. Soc. Trans. 2005, 32 (Pt 5): 742–5. PMID 15494003. doi:10.1042/BST0320742.  Chao C, Hellmich MR. Bi-directional signaling between gastrointestinal peptide hormone receptors and epidermal growth factor receptor. Growth Factors. 2005, 22 (4): 261–8. PMID 15621729. doi:10.1080/08977190412331286900.  Carlsson J, Ren ZP, Wester K; et al. Planning for intracavitary anti-EGFR radionuclide therapy of gliomas. Literature review and data on EGFR expression. J. Neurooncol. 2006, 77 (1): 33–45. PMID 16200342. doi:10.1007/s11060-005-7410-z.  引文格式1维护：显式使用等标签 (link) Scartozzi M, Pierantoni C, Berardi R; et al. Epidermal growth factor receptor: a promising therapeutic target for colorectal cancer. Anal. Quant. Cytol. Histol. 2006, 28 (2): 61–8. PMID 16637508.  引文格式1维护：显式使用等标签 (link) Prudkin L, Wistuba II. Epidermal growth factor receptor abnormalities in lung cancer. Pathogenetic and clinical implications. Annals of diagnostic pathology. 2006, 10 (5): 306–15. PMID 16979526. doi:10.1016/j.anndiagpath.2006.06.011.  Ahmed SM, Salgia R. Epidermal growth factor receptor mutations and susceptibility to targeted therapy in lung cancer. Respirology. 2007, 11 (6): 687–92. PMID 17052295. doi:10.1111/j.1440-1843.2006.00887.x.  Zhang X, Chang A. Somatic mutations of the epidermal growth factor receptor and non-small-cell lung cancer. J. Med. Genet. 2007, 44 (3): 166–72. PMC 2598028 . PMID 17158592. doi:10.1136/jmg.2006.046102.  Cohenuram M, Saif MW. Epidermal growth factor receptor inhibition strategies in pancreatic cancer: past, present and the future. JOP. 2007, 8 (1): 4–15. PMID 17228128.  Mellinghoff IK, Cloughesy TF, Mischel PS. PTEN-mediated resistance to epidermal growth factor receptor kinase inhibitors. Clin. Cancer Res. 2007, 13 (2 Pt 1): 378–81. PMID 17255257. doi:10.1158/1078-0432.CCR-06-1992.  Nakamura JL. The epidermal growth factor receptor in malignant gliomas: pathogenesis and therapeutic implications. Expert Opin. Ther. Targets. 2007, 11 (4): 463–72. PMID 17373877. doi:10.1517/14728222.11.4.463.  醫學主題詞表（MeSH）：Epidermal Growth Factor Receptor