Alectinib在非小细胞肺癌治疗中的研究进展

doi:10.11904/j.issn.1002-3070.2016.01.016

摘要/Abstract

摘要： 目前,分子靶向治疗在非小细胞肺癌(Non-small cell lung cancer,NSCLC)的治疗中占据着重要地位。克唑替尼是第一代ALK酪氨酸激酶抑制剂,于2011年在美国批准上市,用于治疗ALK重排阳性的非小细胞肺癌。然而,克唑替尼仅在治疗的早期阶段有效,长期使用后由于肿瘤出现二次突变而产生耐药。近年来,Alectinib作为第二代ALK激酶抑制剂已经在日本批准上市用于治疗ALK重排阳性的NSCLC患者。本文综述Alectinib在非小细胞肺癌治疗中的研究进展。

关键词: 非小细胞肺癌, 棘皮动物相关样微管蛋白4-间变性淋巴瘤激酶融合基因, 耐药性, 艾乐克替尼, 靶向治疗

Abstract: Recently,targeted therapy plays an important role in the treatment of non-small cell lung cancer.Crizotinib,the first generation of anaplastic lymphoma kinase(ALK)tyrosine kinase inhibitor,has been approved for the treatment of ALK-rearranged NSCLC in the US since 2011.However,the crizotinib therapy is effective only in the early stage of treatment.After a long time treatment,therapy resistance will follow because of the emerging second mutation of the tumor cell.In recent years,as the second generation of anaplastic lymphoma kinase tyrosine kinase inhibitor,alectinib has been approved in Japan for the treatment of ALK-rearranged NSCLC patients.Thus,research progress of Alectinib for NSCLC therapy is summarized in this article.

Key words: Non-small cell lung carcinoma, EML4-ALK, Drug resistance, Alectinib, Target therapy

中图分类号:

R734.1

潘夏综述, 江建平审校. Alectinib在非小细胞肺癌治疗中的研究进展[J]. 实用肿瘤学杂志, 2016, 30(1): 75-79.

PAN Xia, JIANG Jianping. Research progress of Alectinib in the treatment of non-small cell lung cancer[J]. PRACTICAL ONCOLOGY JOURNAL, 2016, 30(1): 75-79.

参考文献

1 Dhillon S.Gefitinib:a review of its use in adults with advanced non-small cell lung cancer[J].Target Oncol,2015,10(1):153-170.
2 D′Arcangelo M,Wynes MW,Hirsch FR.The role of anaplastic lymphoma kinase inhibitors in the treatment of advanced non-small cell lung cancer[J].Curr Opin Oncol,2013,25(2):121-129.
3 Cole P.Alectinib hydrochloride:ALK receptor tyrosine kinase inhibitor oncolytic[J].Drugs Future,2013,38(12):799-805.
4 Shaw AT,Engleman JA.ALK in lung cancer:past,present,and future[J].J Clin Oncol,2013,31(8):1105-1111.
5 Shaw AT,Kim DW,Nakagawa K,et al.Crizotinib versus chemotherapy in advanced ALK-positive lung cancer[J].N Engl J Med,2013,368(25):2385-2394.
6 孔飞飞,姜斌.克里唑替尼在非小细胞肺癌中的研究进展[J].现代肿瘤医学,2013,21(2):433-436.
7 Dziadziuszko R,Jassem J.Beneath the blood brain barrier:the challenge of diagnosis and management of central nervous system involvement in ALK-positive lung cancer[J].J Thorac Oncol,2013,8(12):1465-1466.
8 Awad MM,Sahaw AT.ALK inhibitors in non-small cell lung cancer:crizotinib and beyond[J].Clin Adv Hematol Oncol,2014,12(7):429-439.
9 Dhillon S,Clark M.Ceritinib:first global approval[J].Drugs,2014,74(11):1285-1291.
10 Yoneshima Y,Okamoto I,Takano T,et al.Successful treatment with alectinib after crizotinib-induced esophageal ulceration[J].Lung Cancer,2015,88(3):349-351.
11 Sakamoto H,Tsukaguchi T,Hiroshima S,et al.CH5424802,a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant[J].Cancer Cell,2011,19(5):679-690.
12 Latif M,Saeed A,Kim SH.Journey of the ALK-inhibitor CH5424802 to phase II clinical tria[J].Arch Pharm Res,2013,36(9):1051-1054.
13 Inamura K,Takeuchi K,Togashi Y,et al.EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers[J].J Thorac Oncol,2008,3(1):13-17.
14 Kodama T,Tsukaguchi T,Yoshida M,et al.Selective ALK inhibitor alectinib with potent antitumor activity in models of crizotinib resistance[J].Cancer Lett,2014,351(2):215-221.
15 刘春花,宋勇.克唑替尼在非小细胞肺癌治疗中的研究进展[J].中华肺部疾病杂志,2014,7(1):78-80.
16 Kodama T,Hasegawa M,Takanashi K,et al.Antitumor activity of the selective ALK inhibitor alectinib in models of intracranial metastases[J].Cancer Chemother Pharmacol,2014,74(5):1023-1028.
17 Toyokawa G,Seto T.Updated evidence on the mechanisms of resistance to ALK inhibitors and strategies to overcome such resistance:clinical and preclinical data[J].Oncol Res Treat,2015,38(6):291-298.
18 lqnatius Ou SH,Azada M,Hsiang DJ,et al.Next-generation sequencing reveals a novel NSCLC ALK F1174V mutation and confirms ALK G1202R mutation confers high-level resistance to alectinib(CH5424802/RO5424802)in ALK-rearranged NSCLC patients who progressed on crizotinib[J].J Thorac Oncol,2014,9(4):549-553.
19 Tanimoto A,Yamada T,Nanjo S,et al.Receptor ligand-triggered resistance to alectinib and its circumvention by Hsp90 inhibition in EML4-ALK lung cancer cells[J].Oncotarget,2014,5(13):4920-4928.
20 Seto T,Kiura K,Nishio M,et al.CH5424802(RO5424802)for patients with ALK-rearranged advanced non-small-cell lung cancer(AF-001JP study):a single-arm,open-label,phase 1-2 study[J].Lancet Oncol,2013,14(7):590-598.
21 McKeage K.Alectinib:A review of its use in advanced ALK-rearranged non-small cell lung cancer[J].Drugs,2015,75(2):75-82.
22 Gadgeel SM,Gandhi L,Riely GJ,et al.Safety and activity of alectinib against systemic disease and brain metastases inpatients with crizotinib-resistant ALK-rearranged non-small-cell lung cancer(AF-002JG):results from the dose-finding portion of a phase 1/2 study[J].Lancet Oncol,2014,15(10):1119-1128.
23 Toyokawa G,Seto T.ALK inhibitors:what is the best way to treat patients with ALK⁺ non-small-cell lung cancer?[J].Clin Lung Cancer,2014,15(5):313-319.

[1]	孙立春,李丹丹,李净,于凤玲. CCDC8和TGF-β1在非小细胞肺癌中的表达及临床意义[J]. 实用肿瘤学杂志, 2019, 33(3): 215-221.
[2]	朱琳,张春霞. 纳米载药系统靶向肿瘤干细胞的研究进展[J]. 实用肿瘤学杂志, 2019, 33(3): 276-279.
[3]	李万祯, 殷俊, 李萍, 林晓辉, 张国前, 张书旭. iR-17在非小细胞肺癌放射抗拒细胞中的表达及作用研究[J]. 实用肿瘤学杂志, 2018, 32(5): 391-397.
[4]	蔡静, 候玥. 非小细胞肺癌患者血清miR-195的表达及其临床意义[J]. 实用肿瘤学杂志, 2018, 32(5): 415-419.
[5]	李悦, 徐可, 韩增祥, 孙敏, 樊国华综述, 张勇审校. 结肠癌中肿瘤相关巨噬细胞的作用及靶向治疗的研究进展[J]. 实用肿瘤学杂志, 2018, 32(5): 450-454.
[6]	王元综述, 孙轶华审校. β-连环蛋白在软组织肿瘤中的研究进展[J]. 实用肿瘤学杂志, 2018, 32(5): 455-459.
[7]	崔晓燕, 涂青, 甘建辉. 纳布啡与羟考酮自控镇痛对非小细胞肺癌患者术后免疫因子水平影响的比较[J]. 实用肿瘤学杂志, 2018, 32(4): 309-314.
[8]	雷俊华, 许冠华, 曾江正, 黄芬, 何志惠, 卢彦达. 隐丹参酮联合顺铂抗非小细胞肺癌NCI-H1975细胞JAK2/STAT3机制研究[J]. 实用肿瘤学杂志, 2018, 32(3): 198-202.
[9]	张婷, 贾迪(综述), 杨丹(审校). 骨肉瘤的生物学治疗进展[J]. 实用肿瘤学杂志, 2018, 32(3): 254-257.
[10]	翟可可, 高媛媛, 冯晓, 许静文, 宫玉芳, 孟庆威. 术后辅助化疗后复发转移与初次诊断的IV期NSCLC一线化疗疗效分析[J]. 实用肿瘤学杂志, 2018, 32(2): 107-111.
[11]	杜夜生, 胡松柳, 徐向英. 非小细胞肺癌寡转移的立体定向放射治疗研究[J]. 实用肿瘤学杂志, 2018, 32(2): 154-158.
[12]	孙明亮, 徐建宇, 徐向英. 早期非小细胞肺癌立体定向放疗的相关研究[J]. 实用肿瘤学杂志, 2018, 32(1): 53-56.
[13]	黄倩倩, 马建加, 吴强, 刘彬彬, 沐晓芹, 刘树林审校. 肿瘤干细胞及肿瘤靶向治疗的研究进展[J]. 实用肿瘤学杂志, 2017, 31(6): 533-537.
[14]	黄承路, 韩少辉徐苏琴综述, 赵俊刚审校. 原发性肺黏液腺癌的研究进展[J]. 实用肿瘤学杂志, 2017, 31(5): 463-467.
[15]	代欣综述, 张大昕审校. 非小细胞肺癌抗血管生成治疗研究现状[J]. 实用肿瘤学杂志, 2017, 31(5): 472-476.