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[肺癌的新型生物治疗方法]

[New biological treatments for lung cancer].

作者信息

Zalcman G, Richard N, Bergot E

机构信息

Service de Pneumologie, UFR de Médecine Caen-Basse Normandie, CHU de Caen, avenue de la Côte-de-Nacre, 14033 Caen Cedex 05.

出版信息

Rev Pneumol Clin. 2007 Feb;63(1):20-8. doi: 10.1016/s0761-8417(07)90085-1.

DOI:10.1016/s0761-8417(07)90085-1
PMID:17457280
Abstract

Therapies targeted on cell signal pathways that control cell division and tumor angiogenesis have been developed over the last five years for non small cell lung cancer (NSCLC) with some amazing results, in subgroups of selected patients, predicting more significant success in the upcoming years. Compounds targeted on EGF tyrosine kinase receptor have been tested in large clinical phase 2 and 3 trials including thousands of patients. Their efficacy has been proved, in second and third line trials, after first line cisplatin-based chemotherapy for non-mucinous adenocarcinoma in non-smokers, women and Asian patients. Response rates vary from 10% in non selected Caucasian patients to 40% in non-smoking Asian patients with long survivals. Therapeutic targeting improves success rates, either relying on EGFR gene amplification detection by FISH, or search for EGFR tyrosine kinase domain mutations. Commercial kits are available for routine molecular diagnosis of domain mutations potentially enabling molecular targeting in addition to clinical targeting. Angiogenesis inhibitors, especially monoclonal antibody to VEGF, bevacizumab, have also been developed in the last few years. Bevacizumab associated with classical cytotoxic chemotherapy led, in selected patients (with non squamous cell lung cancer and no past history of cardiovascular disease) to an increase of median survival to more than 12 months with tolerable toxicity. Other drugs that have both anti-EGFR activity and anti-angiogenic properties will be soon developed, since future bioactive anti-cancer drugs will probably be multi-targeted drugs.

摘要

在过去五年中,针对控制细胞分裂和肿瘤血管生成的细胞信号通路开发了多种疗法,用于治疗非小细胞肺癌(NSCLC),并取得了一些惊人的成果。在部分选定患者亚组中,这些疗法显示出显著效果,预示着未来几年将取得更大成功。针对表皮生长因子(EGF)酪氨酸激酶受体的化合物已在包含数千名患者的大型临床2期和3期试验中进行了测试。在针对非吸烟患者、女性患者及亚洲患者的非黏液腺癌进行一线顺铂化疗后的二线和三线试验中,其疗效得到了证实。缓解率从非选定白种人患者的10%到长期存活的非吸烟亚洲患者的40%不等。治疗靶向提高了成功率,这既可以依靠荧光原位杂交(FISH)检测表皮生长因子受体(EGFR)基因扩增,也可以通过寻找EGFR酪氨酸激酶结构域突变来实现。目前已有商业试剂盒可用于常规分子诊断结构域突变,这除了临床靶向之外还可能实现分子靶向。血管生成抑制剂,特别是针对血管内皮生长因子(VEGF)的单克隆抗体贝伐单抗,也在过去几年中得到了开发。在选定患者(非鳞状细胞肺癌且无心血管疾病病史)中,贝伐单抗与传统细胞毒性化疗联合使用可使中位生存期延长至12个月以上,且毒性可耐受。由于未来的生物活性抗癌药物可能是多靶点药物,因此兼具抗EGFR活性和抗血管生成特性的其他药物也将很快被开发出来。

相似文献

1
[New biological treatments for lung cancer].[肺癌的新型生物治疗方法]
Rev Pneumol Clin. 2007 Feb;63(1):20-8. doi: 10.1016/s0761-8417(07)90085-1.
2
[From ASCO and WCLC 2005 to the clinical practice: targeted therapies].[从2005年美国临床肿瘤学会(ASCO)和世界肺癌大会(WCLC)到临床实践:靶向治疗]
Rev Pneumol Clin. 2006 Feb;62 Spec no 1:1S30-4.
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[Targeted therapies. New hopes, new challenges].[靶向治疗。新希望,新挑战]
Rev Mal Respir. 2008 Jun;25(6):661-2. doi: 10.1016/s0761-8425(08)73795-1.
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Targeted therapies in non-small cell lung cancer: proven concepts and unfulfilled promises.非小细胞肺癌的靶向治疗:已证实的概念与未兑现的承诺
Curr Cancer Drug Targets. 2006 Jun;6(4):271-94. doi: 10.2174/156800906777441780.
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Targeted therapy in advanced non-small-cell lung cancer.晚期非小细胞肺癌的靶向治疗
Semin Respir Crit Care Med. 2008 Jun;29(3):291-301. doi: 10.1055/s-2008-1076749.
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Inhibition of the epidermal growth factor receptor in combined modality treatment for locally advanced non-small cell lung cancer.表皮生长因子受体抑制在局部晚期非小细胞肺癌综合治疗中的应用
Semin Oncol. 2005 Apr;32(2 Suppl 3):S35-41. doi: 10.1053/j.seminoncol.2005.03.008.
7
[Targeted therapies in the treatment of non-small cell lung cancer].[非小细胞肺癌治疗中的靶向疗法]
Bull Cancer. 2008 Mar;95(3):358-64. doi: 10.1684/bdc.2008.0591.
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Epidermal growth factor receptor (EGFR) targeted therapies in non-small cell lung cancer (NSCLC).非小细胞肺癌(NSCLC)中的表皮生长因子受体(EGFR)靶向治疗
Rev Recent Clin Trials. 2006 Jan;1(1):1-13. doi: 10.2174/157488706775246157.
9
Investigational agents in the management of non-small cell lung cancer.非小细胞肺癌治疗中的研究性药物
Curr Oncol Rep. 2009 Jul;11(4):275-84. doi: 10.1007/s11912-009-0039-x.
10
Revisiting clinical trials using EGFR inhibitor-based regimens in patients with advanced non-small cell lung cancer: a retrospective analysis of an MD Anderson Cancer Center phase I population.回顾使用基于表皮生长因子受体(EGFR)抑制剂方案治疗晚期非小细胞肺癌患者的临床试验:MD安德森癌症中心I期人群的回顾性分析
Oncotarget. 2013 May;4(5):772-84. doi: 10.18632/oncotarget.1028.

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