Neratinib，為口服製劑，irreversible inhibitor，抑制HER2 and EGFR protein tyrosine kinase(TK)。[5]
酪氨酸激酶抑制剂 Lapatinib Ditosylate (Tykerb®)，口服製劑，和Neratinib相似，一樣是EGFR and HER2 tyrosine kinase的抑制劑。[5]
mTOR 抑制剂 Everolimus (Afinitor®)
相互作用
参考文献
^Olayioye MA. Update on HER-2 as a target for cancer therapy: intracellular signaling pathways of ErbB2/HER-2 and family members. Breast Cancer Res. 2001, 3 (6): 385–389. PMID 11737890. doi:10.1186/bcr327.
^Coussens L. Tyrosine Kinase Receptor with Extensive Homology to EGF Receptor Shares Chromosomal Location with neu Oncogene. Science. 1985, 230: 1132–1139. doi:10.1126/science.2999974.
^Sadeghi, S., Olevsky, O., & Hurvitz, S. A. (2014). Profiling and targeting HER2-positive breast cancer using trastuzumab emtansine. Pharmacogenomics and personalized medicine, 7, 329.
^ 5.05.1Goodman, L. S. (1996). Goodman and Gilman's the pharmacological basis of therapeutics (Vol. 1549). New York: McGraw-Hill.P.1208
深入阅读
Ross JS, Fletcher JA, Linette GP; et al. The Her-2/neu gene and protein in breast cancer 2003: biomarker and target of therapy. Oncologist. 2003, 8 (4): 307–25. PMID 12897328. doi:10.1634/theoncologist.8-4-307. 引文格式1维护：显式使用等标签 (link)
Zhou BP, Hung MC. Dysregulation of cellular signaling by HER2/neu in breast cancer. Semin. Oncol. 2003, 30 (5 Suppl 16): 38–48. PMID 14613025. doi:10.1053/j.seminoncol.2003.08.006.
Ménard S, Casalini P, Campiglio M; et al. Role of HER2/neu in tumor progression and therapy. Cell. Mol. Life Sci. 2005, 61 (23): 2965–78. PMID 15583858. doi:10.1007/s00018-004-4277-7. 引文格式1维护：显式使用等标签 (link)
Becker JC, Muller-Tidow C, Serve H; et al. Role of receptor tyrosine kinases in gastric cancer: new targets for a selective therapy. World J. Gastroenterol. 2006, 12 (21): 3297–305. PMID 16733844. 引文格式1维护：显式使用等标签 (link)
Laudadio J, Quigley DI, Tubbs R, Wolff DJ. HER2 testing: a review of detection methodologies and their clinical performance. Expert Rev. Mol. Diagn. 2007, 7 (1): 53–64. PMID 17187484. doi:10.1586/14737159.7.1.53.
Bianchi F, Tagliabue E, Ménard S, Campiglio M. Fhit expression protects against HER2-driven breast tumor development: unraveling the molecular interconnections. Cell Cycle. 2007, 6 (6): 643–6. PMID 17374991. doi:10.4161/cc.6.6.4033.
Del Bimbo A., Meoni M., Pala P. Accurate evaluation of HER-2 amplification in FISH images. Imaging Systems and Techniques (IST), 2010 IEEE International Conference on. 2010: 407–10. ISBN 978-1-4244-6492-0. doi:10.1109/IST.2010.5548461.
外部链接
ERBB2 expression across human cancerous and healthy tissues[永久失效連結]
her2, 人类表皮生长因子受体2, 英語, human, epidermal, growth, factor, receptor, 缩写为her2, 亦称为neu, erbb, cd340, 分化群340, 或p185, 是一种由erbb2基因编码的蛋白质, her2是表皮生长因子受体, egfr, erbb, 家族的成员, receptor, tyrosine, kinase, 2pdb繪製基於1n8z, 曲妥珠單抗fab片段, 藍色, 結合到her2, 米色, 的胞外域, 有效结构pdb, 直系同源检索, p. 人类表皮生长因子受体2 英語 human epidermal growth factor receptor 2 缩写为HER2 亦称为Neu ErbB 2 CD340 分化群340 或p185 是一种由ERBB2基因编码的蛋白质 HER2是表皮生长因子受体 EGFR ErbB 家族的成员 Erb b2 receptor tyrosine kinase 2PDB繪製基於1n8z 曲妥珠單抗Fab片段 藍色 結合到HER2 米色 的胞外域 有效结构PDB 直系同源检索 PDBe RCSBPDB查询代码列表1MFG 1MFL 1MW4 1N8Z 1QR1 1S78 2A91 2JWA 2KS1 2L4K 3BE1 3H3B 3MZW 3N85 3PP0 3RCD标识代号ERBB2 CD340 HER 2 HER 2 neu HER2 MLN 19 NEU NGL TKR1扩展标识遗传学 164870 鼠基因 95410 同源基因 3273 ChEMBL 1824 GeneCards ERBB2 GeneEC編號2 7 10 1基因本体论描述分子功能 RNA polymerase I core binding protein tyrosine kinase activity transmembrane receptor protein tyrosine kinase activity receptor signaling protein tyrosine kinase activity transmembrane signaling receptor activity epidermal growth factor activated receptor activity protein binding ATP binding protein C terminus binding growth factor binding protein phosphatase binding identical protein binding ErbB 3 class receptor binding protein heterodimerization activity protein dimerization activity细胞成分 nucleus plasma membrane endosome membrane integral to membrane basolateral plasma membrane apical plasma membrane receptor complex perinuclear region of cytoplasm生物过程 positive regulation of protein phosphorylation transcription DNA dependent protein phosphorylation signal transduction cell surface receptor signaling pathway enzyme linked receptor protein signaling pathway transmembrane receptor protein tyrosine kinase signaling pathway epidermal growth factor receptor signaling pathway nervous system development axon guidance peripheral nervous system development heart development neuromuscular junction development motor neuron axon guidance cell proliferation fibroblast growth factor receptor signaling pathway phosphatidylinositol 3 kinase cascade signal transduction by phosphorylation positive regulation of cell growth mammary gland development positive regulation of Rho GTPase activity regulation of microtubule based process negative regulation of immature T cell proliferation in thymus wound healing myelination positive regulation of MAP kinase activity innate immune response positive regulation of translation regulation of angiogenesis positive regulation of cell adhesion positive regulation of transcription from RNA polymerase I promoter positive regulation of transcription from RNA polymerase III promoter protein autophosphorylation neurotrophin TRK receptor signaling pathway phosphatidylinositol mediated signaling positive regulation of epithelial cell proliferation regulation of ERK1 and ERK2 cascadeSources Amigo QuickGORNA表达模式更多表达数据直系同源体物种人类小鼠Entrez206413866EnsemblENSG00000141736ENSMUSG00000062312UniProtP04626P70424mRNA序列NM 001005862NM 001003817蛋白序列NP 001005862NP 001003817基因位置Chr 17 37 84 37 89 MbChr 11 98 41 98 44 MbPubMed查询 1 2 查论编 目录 1 功能 2 與癌症的關係 3 針对HER2的葯物 4 相互作用 5 参考文献 6 深入阅读 7 外部链接功能 编辑HER2是结合在细胞膜表面的受体酪氨酸激酶 参与导致细胞生长和分化的信号传导途径 由原癌基因HER2 neu编码 一般认为HER2是一个孤受体 表皮生长因子家族的配体都不能激活它 但配体结合ErbB受体时可形成二聚体 且HER2可与ErbB家族的其他成员结合成异二聚体 1 HER2基因是原癌基因 位于人类17号染色体长臂 17q21 q22 2 與癌症的關係 编辑HER 2基因是影響乳癌預後的一個重要因素 大約有25 30 左右的乳癌患者 受到體內癌細胞HER 2基因過量表現的影響 他們的癌細胞不僅繁殖能力強 對部份化學治療藥物也容易有抗藥性 造成病患即使接受手術治療 癌細胞仍然有較高復發及轉移的機率 無法長期存活 乳癌病患可分為Her 2 neu陽性或Her 2 neu陰性兩種截然不同的預後之乳癌 乳癌患者的腫瘤 若HER 2蛋白質出現過量表現 這類的腫瘤生長速度較快且生物行為較為惡性 使得手術後復發率高於其他類型的乳癌 3 表皮生長因子受體 EGFR 信號傳導級聯針对HER2的葯物 编辑羅氏藥廠開發的賀癌平 Herceptin 即是以HER2為标靶的葯物 對晚期转移性的乳腺癌頗具效用 重组型人源化单克隆抗体 Trastuzumab Herceptin 是IgG1 monoclonal antibody 可透過結合到乳癌細胞膜上的HER2 receptor的Domain4去抑制下游的hetero and homodimerization和信號傳遞 完全人源化单克隆抗体 Pertuzumab Perjeta 和Trastuzumab藥理作用位點相似 但Pertuzumab 是結合在HER2的Domain2 去抑制下游路徑 而且因為Domain2是屬於extracellular receptor dimerization 因此可防止其他的HER family members和HER2進行dimerization 從而抑制了ligand induced signaling 抑制了細胞生長而進行細胞凋亡 其中HER2 HER3被认为是下游通路激活的最强二聚体 单抗结合型药物 Ado Trastuzumab emtansine Kadcyla 為新藥 是一種Antibody和Drug的conjugate ADC Trastuzumab上述已介紹過他的作用位點 而新藥T DM1則是將Trastuzumab和maytansine 1用thioether鍵結起來 DM1即derivative of maytansine 1 是一種合成Microtubule 過程中dimerization的抑制劑 將Trastuzumab和cytotoxic agent DM1結合 除了有Trastuzumab本身能夠與HER2 receptor Domain4結合 進而停止了癌細胞的生長 DM1透過receptor mediated進入細胞內作用 並在lysosome內代謝 釋放出含DM1的代謝產物 此物質可結合在Microtubule上 導致有絲分裂終止和細胞死亡 4 Neratinib 為口服製劑 irreversible inhibitor 抑制HER2 and EGFR protein tyrosine kinase TK 5 酪氨酸激酶抑制剂 Lapatinib Ditosylate Tykerb 口服製劑 和Neratinib相似 一樣是EGFR and HER2 tyrosine kinase的抑制劑 5 mTOR 抑制剂 Everolimus Afinitor 相互作用 编辑参考文献 编辑 Olayioye MA Update on HER 2 as a target for cancer therapy intracellular signaling pathways of ErbB2 HER 2 and family members Breast Cancer Res 2001 3 6 385 389 PMID 11737890 doi 10 1186 bcr327 Coussens L Tyrosine Kinase Receptor with Extensive Homology to EGF Receptor Shares Chromosomal Location with neu Oncogene Science 1985 230 1132 1139 doi 10 1126 science 2999974 HER 2陽性早期乳癌治療的近況 台灣癌症防治網 2009年10月16日 2009 10 06 原始内容存档于2011年5月25日 Sadeghi S Olevsky O amp Hurvitz S A 2014 Profiling and targeting HER2 positive breast cancer using trastuzumab emtansine Pharmacogenomics and personalized medicine 7 329 5 0 5 1 Goodman L S 1996 Goodman and Gilman s the pharmacological basis of therapeutics Vol 1549 New York McGraw Hill P 1208深入阅读 编辑Ross JS Fletcher JA Linette GP et al The Her 2 neu gene and protein in breast cancer 2003 biomarker and target of therapy Oncologist 2003 8 4 307 25 PMID 12897328 doi 10 1634 theoncologist 8 4 307 引文格式1维护 显式使用等标签 link Zhou BP Hung MC Dysregulation of cellular signaling by HER2 neu in breast cancer Semin Oncol 2003 30 5 Suppl 16 38 48 PMID 14613025 doi 10 1053 j seminoncol 2003 08 006 Menard S Casalini P Campiglio M et al Role of HER2 neu in tumor progression and therapy Cell Mol Life Sci 2005 61 23 2965 78 PMID 15583858 doi 10 1007 s00018 004 4277 7 引文格式1维护 显式使用等标签 link Becker JC Muller Tidow C Serve H et al Role of receptor tyrosine kinases in gastric cancer new targets for a selective therapy World J Gastroenterol 2006 12 21 3297 305 PMID 16733844 引文格式1维护 显式使用等标签 link Laudadio J Quigley DI Tubbs R Wolff DJ HER2 testing a review of detection methodologies and their clinical performance Expert Rev Mol Diagn 2007 7 1 53 64 PMID 17187484 doi 10 1586 14737159 7 1 53 Bianchi F Tagliabue E Menard S Campiglio M Fhit expression protects against HER2 driven breast tumor development unraveling the molecular interconnections Cell Cycle 2007 6 6 643 6 PMID 17374991 doi 10 4161 cc 6 6 4033 Del Bimbo A Meoni M Pala P Accurate evaluation of HER 2 amplification in FISH images Imaging Systems and Techniques IST 2010 IEEE International Conference on 2010 407 10 ISBN 978 1 4244 6492 0 doi 10 1109 IST 2010 5548461 外部链接 编辑ERBB2 expression across human cancerous and healthy tissues 永久失效連結 AACR Cancer Concepts Factsheet on HER2 Her2 neu Vaccine Protects Against Tumor Growth Chimeric molecules and Methods of Use Breast Friends for Life Network A South African Breast Cancer Support Forum for HER2 Positive Women 醫學主題詞表 MeSH Receptor erbB 2 取自 https zh wikipedia org w index php title HER2 neu amp oldid 73840255, 维基百科，wiki，书籍，书籍，图书馆，
