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中华胸部外科电子杂志 ›› 2017, Vol. 04 ›› Issue (01) : 56 -62. doi: 10.3877/cma.j.issn.2095-8773.2017.01.11

所属专题: 文献

综述

表皮生长因子受体相关靶向治疗与肺癌的研究进展
王丹云1,(), 彭忠民2   
  1. 1. 250013 山东大学附属济南市中心医院普胸外科
    2. 250021 山东大学附属省立医院普胸外科
  • 收稿日期:2016-10-14 出版日期:2017-02-28
  • 通信作者: 王丹云

Research progress of EGFR related targeted therapy and pulmonary carcinoma

Danyun Wang1,(), Zhongmin Peng2   

  1. 1. Department of General Thoracic Surgery, Jinan Center Hospital affiliated to Shandong University, Jinan 250013, China
    2. Department of General Thoracic Surgery, Shandong Provincial Hospital affiliated to Shandong University, Jinan250021, China
  • Received:2016-10-14 Published:2017-02-28
  • Corresponding author: Danyun Wang
  • About author:
    Corresponding author: Wang Danyun, Email:
引用本文:

王丹云, 彭忠民. 表皮生长因子受体相关靶向治疗与肺癌的研究进展[J]. 中华胸部外科电子杂志, 2017, 04(01): 56-62.

Danyun Wang, Zhongmin Peng. Research progress of EGFR related targeted therapy and pulmonary carcinoma[J]. Chinese Journal of Thoracic Surgery(Electronic Edition), 2017, 04(01): 56-62.

近年来,非小细胞肺癌(NSCLC)的治疗进展主要以分子靶向治疗为主导地位。依据组织和分子学类型制定个体化治疗方案已成为靶向治疗时代的准则,表皮生长因子受体(EGFR)基因是目前肺癌众多驱动基因中研究最多、证据最充分、了解最透彻的一个分子靶点。表皮生长因子酪氨酸激酶抑制剂(EGFR-TKI)已广泛应用于EGFR突变的NSCLC。该文将EGFR相关靶向药物在NSCLC的治疗进展做一综述。

During the past several years, advances in the treatment of non-small cell lung cancer (NSCLC) have predominantly involved the development of therapies directed at molecular targets. Treatment based on histology and molecular characterization has become a guideline of care in the era of targeted therapy. Among numerous driver genes of NSCLC, epidermal growth factor receptor(EGFR) gene is one molecular target concerning with most researches, abundant evidences and thorough understandings. Epidermal growth factor tyrosine kinase inhibitor (EGFR-TKI) has been widely used in the treatment of NSCLC haboring EGFR mutation. This review provides an overview of current EGFR gene related targeted therapies in NSCLC.

1
Prenzel N, Fischer OM, Streit S, et al. The epidermal growth factor receptor family as a central element for cellular signal transduction and diversification[J].Endocr Relat Cancer, 2001, 8(1):11-31.
2
Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network[J].Nat Rev Mol Cell Biol, 2001, 2(2):127-137.
3
Sordella R, Bell DW, Haber DA, et al. Gefitinib-sensitizing EGFR mutations in lung cancer activate anti-apoptotic pathways[J].Science,2004, 305(5687):1163-1167.
4
Yano M, Sasaki H, Kobayashi Y, et al. Epidermal growth factor receptor gene mutation and computed tomographic findings in peripheral pulmonary adenocarcinoma[J].J Thorac Oncol, 2006, 1(5):413-416.
5
Rosell R, Carcereny E, Gervais R, et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial[J].Lancet Oncol, 2012, 13(3):239-246.
6
Goto K, Ichinose Y, Ohe Y, et al. Epidermal growth factor receptor mutation status in circulating free DNA in serum: from IPASS, a phase Ⅲ study of gefitinib or carboplatin/paclitaxel in non-small cell lung cancer[J].J Thorac Oncol,2012, 7(1):115-121.
7
Mitsudomi T, Morita S, Yatabe Y, et al. Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial[J].Lancet Oncol, 2010, 11(2):121-128.
8
Pirker R, Pereira JR, von Pawel J, et al. EGFR expression as a predictor of survival for first-line chemotherapy plus cetuximab in patients with advanced non-small-cell lung cancer: analysis of data from the phase 3 FLEX study[J].Lancet Oncol,2012, 13(1):33-42.
9
Tamura K, Fukuoka M. Molecular target-based cancer  therapy: tyrosine kinase inhibitors[J].Int J Clin Oncol, 2003, 8(4):207-211.
10
Thatcher N, Chang A, Parikh P, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: results from a randomised, placebo-controlled, multicentre study (Iressa Survival Evaluation in Lung Cancer)[J].Lancet, 2005, 366(9496):1527-1537.
11
Chang A, Parikh P, Thongprasert S, et al. Gefitinib (IRESSA) in patients of Asian origin with refractory advanced non-small cell lung cancer: subset analysis from the ISEL study[J].J Thorac Oncol, 2006, 1(8):847-855.
12
Shepherd FA, Rodrigues Pereira J, Ciuleanu T, et al. Erlotinib in previously treated non-small-cell lung cancer[J].N Engl J Med,2005, 353(2):123-132.
13
Kim ES, Hirsh V, Mok T, et al. Gefitinib versus docetaxel in previously treated non-small-cell lung cancer (INTEREST): a randomised phase Ⅲ trial[J].Lancet, 2008, 372(9652):1809-1818.
14
Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma[J].N Engl J Med, 2009, 361(10):947-957.
15
Maemondo M, Inoue A, Kobayashi K, et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR[J].N Engl J Med, 2010, 362(25):2380-2388.
16
Zhou C, Wu YL, Chen G, et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study[J].Lancet Oncol,2011, 12(8):735-742.
17
Sequist LV, Yang JC, Yamamoto N, et al. Phase Ⅲ study of afatinib or cisplatin plus pemetrexed in patients with metastatic lung adenocarcinoma with EGFR mutations[J].J Clin Oncol, 2013, 31(27):3327-3334.
18
Wu YL, Zhou C, Hu CP, et al. Afatinib versus cisplatin plus gemcitabine for first-line treatment of Asian patients with advanced non-small-cell lung cancer harbouring EGFR mutations (LUX-Lung 6): an open-label, randomised phase 3 trial[J].Lancet Oncol,2014, 15(2):213-222.
19
Goss GD, O'Callaghan C, Lorimer I, et al. Gefitinib versus placebo in completely resected non-small-cell lung cancer: results of the NCIC CTG BR19 study[J].J Clin Oncol, 2013, 31(27):3320-3326.
20
Janjigian YY, Park BJ, Zakowski MF, et al. Impact on disease-free survival of adjuvant erlotinib or gefitinib in patients with resected lung adenocarcinomas that harbor EGFR mutations[J].J Thorac Oncol, 2011, 6(3):569-575.
21
Li N, Ou W, Ye X, et al. Pemetrexed-carboplatin adjuvant chemotherapy with or without gefitinib in resected stage ⅢA-N2 non-small cell lung cancer harbouring EGFR mutations: a randomized, phase Ⅱ study[J].Ann Surg Oncol, 2014, 21(6):2091-2096.
22
Kelly K, Altorki NK, Eberhardt WE, et al. Adjuvant Erlotinib Versus Placebo in Patients With Stage IB-ⅢA Non-Small-Cell Lung Cancer (RADIANT): A Randomized, Double-Blind, Phase Ⅲ Trial[J].J Clin Oncol, 2015, 33(34):4007-4014.
23
Lampaki S, Lazaridis G, Zarogoulidis K, et al. Defining the role of tyrosine kinase inhibitors in early stage non-small cell lung cancer[J].J Cancer, 2015, 6(6):568-574.
24
Huang Q, Li J, Sun Y, et al. Efficacy of EGFR tyrosine kinase inhibitors in the adjuvant eatment for operable non-small cell lung cancer by a meta-analysis[J].Chest, 2016, 149(6):1384-1392.
25
Herbst RS, Prager D, Hermann R, et al. TRIBUTE: a phase Ⅲ trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer[J].J Clin Oncol,2005, 23(25):5892-5899.
26
Gatzemeier U, Pluzanska A, Szczesna A, et al. Phase Ⅲ study of erlotinib in combination with cisplatin and gemcitabine in advanced non-small-cell lung cancer: the Tarceva Lung Cancer Investigation Trial[J].J Clin Oncol, 2007, 25(12):1545-1552.
27
Herbst RS, Giaccone G, Schiller JH, et al. Gefitinib in combination with paclitaxel and carboplatin in advanced non-small-cell lung cancer: a phase Ⅲ trial--INTACT 2[J].J Clin Oncol,2004, 22(5):785-794.
28
Giaccone G, Herbst RS, Manegold C, et al. Gefitinib in combination with gemcitabine and cisplatin in advanced non-small-cell lung cancer: a phase Ⅲ trial--INTACT 1[J].J Clin Oncol,2004, 22(5):777-784.
29
Wu YL, Lee JS, Thongprasert S, et al. Intercalated combination of chemotherapy and erlotinib for patients with advanced stage non-small-cell lung cancer (FASTACT-2): a randomised, double-blind trial[J].Lancet Oncol, 2013, 14(8):777-786.
30
Sugawara S, Oizumi S, Minato K, et al. Randomized phase Ⅱ study of concurrent versus sequential alternating gefitinib and chemotherapy in previously untreated non-small cell lung cancer with sensitive EGFR mutations: NEJ005/TCOG0902[J].Ann Oncol, 2015, 26(5):888-894.
31
Cheng Y, Murakami H, Yang PC, et al. Randomized phase Ⅱ trial of Gefitinib with and without pemetrexed as first-line therapy in patients with advanced nonsquamous non-small-cell lung cancer with activating epidermal growth factor receptor mutations[J].J Clin Oncol, 2016,34(27):3258-3266.
32
Seto T, Kato T, Nishio M, et al. Erlotinib alone or with bevacizumab as first-line therapy in patients with advanced non-squamous non-small-cell lung cancer harbouring EGFR mutations (JO25567): an open-label, randomised, multicentre, phase 2 study[J].Lancet Oncol, 2014, 15(11):1236-1244.
33
Janne PA, Yang JC, Kim DW, et al. AZD9291 in EGFR inhibitor-resistant non-small-cell lung cancer[J].N Engl J Med, 2015, 372(18):1689-1699.
34
Sequist LV, Soria JC, Goldman JW, et al. Rociletinib in EGFR-mutated non-small-cell lung cancer[J].N Engl J Med, 2015, 372(18):1700-1709.
35
Wang W, Li Q, Takeuchi S, et al. Met kinase inhibitor E7050 reverses three different mechanisms of hepatocyte growth factor-induced tyrosine kinase inhibitor resistance in EGFR mutant lung cancer[J].Clin Cancer Res, 2012, 18(6):1663-1671.
36
Nakagawa T, Takeuchi S, Yamada T, et al. Combined therapy with mutant-selective EGFR inhibitor and Met kinase inhibitor for overcoming erlotinib resistance in EGFR-mutant lung cancer[J].Mol Cancer Ther, 2012, 11(10):2149-2157.
37
Gou LY, Li AN, Yang JJ, et al. The coexistence of MET over-expression and an EGFR T790M mutation is related to acquired resistance to EGFR tyrosine kinase inhibitors in advanced non-small cell lung cancer[J]. Oncotarget, 2016,7(32):51311-51319.
38
Tan DS, Yom SS, Tsao MS, et al. The International Association for the Study of Lung Cancer Consensus Statement on Optimizing Management of EGFR Mutation-Positive Non-Small Cell Lung Cancer: Status in 2016[J].J Thorac Oncol, 2016, 11(7):946-963.
39
Hata A, Katakami N, Yoshioka H, et al. Prognostic impact of central nervous system metastases after acquired resistance to EGFR-TKI: poorer prognosis associated with T790M-negative status and leptomeningeal metastases[J].Anticancer Res, 2015, 35(2):1025-1031.
40
Li YS, Jiang BY, Yang JJ, et al. Leptomeningeal metastases in patients with NSCLC with EGFR mutations[J]. J Thorac Oncol,2016,11(11):1962-1969.
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