表皮生長因子受體單克隆抗體耐藥機制研究的新進展_《華西醫學》

作者：

李榮惠 ¹ , 唐秋琳 ² ,  畢鋒 ^1,2

四川大學（成都，610041）1華西醫院腹部腫瘤科，2生物治療國家重點實驗室信號轉導及分子靶向治療研究室;

關鍵詞：

表皮生長因子受體靶向治療藥物耐受

DOI：

10.7507/1002-0179.20130459

視頻：

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表皮生長因子受體（EGFR）是HER家族中一類表皮生長因子酪氨酸激酶受體，其下游的信號通路調控著細胞的生長、增殖、分化、侵襲、遷移、血管形成等生物學行為。EGFR在上皮源性腫瘤中常有表達，在近幾十年中，將EGFR作為抗腫瘤治療的靶點，研制出一系列靶向治療藥物，主要有小分子酪氨酸激酶抑制劑和單克隆抗體這兩大類。然而，在結直腸癌中EGFR單克隆抗體靶向治療的有效率卻不高，原發和繼發性耐藥成為阻礙靶向藥物應用的關鍵因素。由此推動了關于靶向藥物各種耐藥機制的研究，現就近兩年來EGFR單克隆抗體耐藥機制研究的新進展作一綜述。

引用本文： 李榮惠,唐秋琳,畢鋒. 表皮生長因子受體單克隆抗體耐藥機制研究的新進展. 華西醫學, 2013, 28(9): 1465-1467. doi: 10.7507/1002-0179.20130459 復制

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13.	Ciardiello F, Bianco R, Caputo R, et al. Antitumor activity of ZD6474, a vascular endothelial growth factor receptor tyrosine kinase inhibitor, in human cancer cells with acquired resistance to antiepidermal growth factor receptor therapy[J]. Clin Cancer Res, 2004, 10(2): 784-793.
14.	Lu Y, Li X, Liang K, et al. Epidermal growth factor receptor (EGFR) ubiquitination as a mechanism of acquired resistance escaping treatment by the anti-EGFR monoclonal antibody cetuximab[J]. Cancer Res, 2007, 67(17): 8240-8247.
15.	Wheeler DL, Iida M, Kruser TJ, et al. Epidermal growth factor receptor cooperates with Src family kinases in acquired resistance to cetuximab[J]. Cancer Biol Ther, 2009, 8(8): 696-703.
16.	Huang S, Benavente S, Armstrong EA, et al. p53 modulates acquired resistance to EGFR inhibitors and radiation[J]. Cancer Res, 2011, 71(22): 7071-7079.
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24.	Johansson AC, Ansell A, Jerhammar F, et al. cancer-associated fibroblasts induce matrix metalloproteinase-mediated cetuximab resistance in head and neck squamous cell carcinoma cells[J]. Mol Cancer Res, 2012, 10(9): 1158-1168.

1. 　Marmor MD, Skaria KB, Yarden Y. Signal transduction and oncogenesis by ErbB/HER receptors[J]. Int J Radiat Oncol Biol Phys, 2004, 58(3): 903-913.
2. 　Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network[J]. Nat Rev Mol Cell Biol, 2001, 2(2): 127-137.
3. 　Sato JD, Kawamoto T, Le AD, et al. Biological effects in vitro of monoclonal antibodies to human epidermal growth factor receptors[J]. Mol Biol Med, 1983, 1(5): 511-529.
4. 　Camp ER, Summy J, Bauer TW, et al. Molecular mechanisms of resistance to therapies targeting the epidermal growth factor receptor[J]. Clin Cancer Res, 2005, 11(1): 397-405.
5. 　Vecchione L, Jacobs B, Normanno N, et al. EGFR-targeted therapy[J]. Exp Cell Res, 2011, 317(19): 2765-2771.
6. 　Bokemeyer C, Bondarenko I, Makhson A, et al. Fluorouracil, leucovorin, and oxaliplatin with and without cetuximab in the first-line treatment of metastatic colorectal cancer[J]. J Clin Oncol, 2009, 27(5): 663-671.
7. 　Van Cutsem E, Köhne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer[J]. N Engl J Med, 2009, 360(14): 1408-1417.
8. 　Jy D, Siena S, Cassidy J, et al. Randomized, phaseⅢ trial of panitumumab with infusional fluorouracil,leucovorin,and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study[J]. J Clin Oncol, 2010, 28(31): 4697-4705.
9. 　Wheeler DL, Huang S, Kruser TJ, et al. Mechanisms of acquired resistance to cetuximab: role of HER (ErbB) family members[J]. Oncogene, 2008, 27(28): 3944-3956.
10. 　Rajput A, Koterba AP, Kreisberg JI, et al. A novel mechanism of resistance to epidermal growth factor receptor antagonism in vivo[J]. Cancer Res, 2007, 67(2): 665-673.
11. 　Viloria-Petit A, Crombet T, Jothy S, et al. Acquired resistance to the antitumor effect of epidermal growth factor receptor-blocking antibodies in vivo: a role for altered tumor angiogenesis[J]. Cancer Res, 2001, 61(13): 5090-5101.
12. 　Bianco R, Rosa R, Damiano V, et al. Vascular endothelial growth factor receptor-1 contributes to resistance to anti-epidermal growth factor receptor drugs in human cancer cells[J]. Clin Cancer Res, 2008, 14(16): 5069-5080.
13. 　Ciardiello F, Bianco R, Caputo R, et al. Antitumor activity of ZD6474, a vascular endothelial growth factor receptor tyrosine kinase inhibitor, in human cancer cells with acquired resistance to antiepidermal growth factor receptor therapy[J]. Clin Cancer Res, 2004, 10(2): 784-793.
14. 　Lu Y, Li X, Liang K, et al. Epidermal growth factor receptor (EGFR) ubiquitination as a mechanism of acquired resistance escaping treatment by the anti-EGFR monoclonal antibody cetuximab[J]. Cancer Res, 2007, 67(17): 8240-8247.
15. 　Wheeler DL, Iida M, Kruser TJ, et al. Epidermal growth factor receptor cooperates with Src family kinases in acquired resistance to cetuximab[J]. Cancer Biol Ther, 2009, 8(8): 696-703.
16. 　Huang S, Benavente S, Armstrong EA, et al. p53 modulates acquired resistance to EGFR inhibitors and radiation[J]. Cancer Res, 2011, 71(22): 7071-7079.
17. 　Rosa R, Marciano R, Malapelle U, et al. Sphingosine kinase 1 overexpression contributes to cetuximab resistance in human colorectal cancer models[J]. Clin Cancer Res, 2013, 19(1): 138-147.
18. 　Yamada T, Takeuchi S, Kita K, et al. Hepatocyte growth factor induces resistance to anti-epidermal growth factor receptor antibody in lung cancer[J]. J Thorac Oncol, 2012, 7(2): 272-280.
19. 　Liska D, Chen CT, Bachleitner-Hofmann T, et al. HGF rescues colorectal cancer cells from EGFR inhibition via Met activation[J]. Clin cancer Res, 2011, 17(3): 472-482.
20. 　Sen M, Joyce S, Panahandeh M, et al. Targeting Stat3 abrogates EGFR inhibitor resistance in cancer[J]. Clin cancer Res, 2012, 18(18): 4986-4996.
21. 　de Farias CB, Heinen TE, dos Santos RP, et al. BDNF/TrkB signaling protects HT-29 human colon cancer cells from EGFR inhibition[J]. Biochem Biophys Res Commun, 2012, 425(2): 328-332.
22. 　Pandey JP. Mechanism of resistance to cetuximab therapy in colorectal cancer: possible role of antibodies to immunoglobulin allotypes[J]. MABS, 2012, 4(5): 553-554.
23. 　Ogawa T, Liggett TE, Melnikov AA, et al. Methylation of death-associated protein kinase is associated with cetuximab and erlotinib resistance[J]. Cell Cycle, 2012, 11(8): 1656-1663.
24. 　Johansson AC, Ansell A, Jerhammar F, et al. cancer-associated fibroblasts induce matrix metalloproteinase-mediated cetuximab resistance in head and neck squamous cell carcinoma cells[J]. Mol Cancer Res, 2012, 10(9): 1158-1168.

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《華西醫學》

表皮生長因子受體單克隆抗體耐藥機制研究的新進展

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