ALK基因在非小细胞肺癌中的研究进展

doi:10.3760/cma.j.issn.1673-422X.2014.08.011

摘要/Abstract

摘要： 靶向治疗是目前非小细胞肺癌（NSCLC）中最具前景的研究方向。继表皮生长因子受体（EGFR）之后，间变性淋巴瘤激酶(ALK)有望成为NSCLC治疗的新靶点，而相关研究提示ALK抑制剂（如克唑替尼）在ALK基因重排阳性的NSCLC患者中有较好疗效。因此探明ALK基因的检测方法、临床病理特征以及了解ALK抑制剂的研究进展对NSCLC的个体化治疗十分重要。

关键词: 癌, 非小细胞肺, 间变性淋巴瘤激酶, 分子靶向治疗

Abstract: Targeted therapy is the most prospective part of the research related to the treatment of nonsmall cell lung cancer (NSCLC). After epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK) gene is expected to become a new target in the treatment of NSCLC. Moreover, several related researches suggest that ALK inhibitor (crizotinib) is effective for treatment of ALKrearranged NSCLC. Therefore, it is important to review the detection method of ALK gene, clinicopathologic features and the research progress of ALK inhibitor for the individual treatment of NSCLC.

Key words: Carcinoma, non-small-cell lung, Anaplastic lymphoma kinase, Molecular targeted therapy

房姝,潘志峰. ALK基因在非小细胞肺癌中的研究进展[J]. 国际肿瘤学杂志, 2014, 41(8): 592-594.

Fang Shu, Pan Zhifeng. Advances of anaplastic lymphoma kinase in non-small cell lung cancer[J]. Journal of International Oncology, 2014, 41(8): 592-594.

参考文献

［1］ Reck M, von Pawel J, Zatloukal P, et al. Phase Ⅲ trial of cisplatin plus gemcitabine with either placebo or bevacizumab as firstline therapy for nonsquamous nonsmallcell lung cancer: AVAil［J］. J Clin Oncol, 2009, 27(8): 1227-1234. ［2］ Morris SW, Kirstein MN, Valentine MB, et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in nonHodgkin′s lymphoma［J］. Science, 1994, 263(5151): 1281-1284. ［3］ Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4ALK fusion gene in nonsmallcell lung cancer［J］. Nature, 2007, 448 (7153): 561-566. ［4］ Zhang S, Wang F, Keats J, et al. Crizotinibresistant mutants of EML4ALK identified through an accelerated mutagenesis screen［J］. Chem Biol Drug Des, 2011, 78 (6): 999-1005. ［5］ Weickhardt AJ, Aisner DL, Franklin WA, et al. Diagnostic assays for identification of anaplastic lymphoma kinasepositive nonsmall cell lung cancer［J］. Cancer, 2013, 119(8): 1467-1477. ［6］ MinoKenudson M, Chirieac LR, Law K, et al. A novel, highly sensitive antibody allows for the routine detection of ALKrearranged lung adenocarcinomas by standard immunohistochemistry［J］. Clin Cancer Res, 2010, 16(5): 1561-1571. ［7］ Sun JM, Choi YL, Won JK, et al. A dramatic response to crizotinib in a nonsmallcell lung cancer patient with IHCpositive and FISHnegative ALK［J］. J Thorac Oncol, 2012, 7(12): e36-38. ［8］ Wallander ML, Geiersbach KB, Tripp SR, et al. Comparison of reverse transcriptionpolymerase chain reaction, immunohistochemistry, and fluorescence in situ hybridization methodologies for detection of echinoderm microtubuleassociated proteinlike 4anaplastic lymphoma kinase fusionpositive nonsmall cell lung carcinoma: implications for optimal clinical testing［J］. Arch Pathol Lab Med, 2012, 136(7): 796-803. ［9］ Camidge DR, Bang YJ, Kwak EL, et al. Activity and safety of crizotinib in patients with ALKpositive nonsmallcell lung cancer: updated results from a phase 1 study［J］. Lancet Oncol, 2012, 13(10): 1011-1019. ［10］ Shaw AT, Yeap BY, MinoKenudson M, et al. Clinical features and outcome of patients with nonsmallcell lung cancer who harbor EML4ALK［J］. J Clin Oncol, 2009, 27(26): 4247-4253. ［11］ Rodig SJ, MinoKenudson M, Dacic S, et al. Unique clinicopathologic features characterize ALKrearranged lung adenocarcinoma in the western population［J］. Clin Cancer Res, 2009, 15(16): 5216-5223. ［12］ 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. ［13］ Wong DW, Leung EL, So KK, et al. The EML4ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wildtype EGFR and KRAS［J］. Cancer, 2009, 115(8): 1723-1733. ［14］ Zhang X, Zhang S, Yang X, et al. Fusion of EML4 and ALK is associated with development of lung adenocarcinomas lacking EGFR and KRAS mutations and is correlated with ALK expression［J］. Mol Cancer, 2010, 9: 188. ［15］ Kris MG, Johnson BE, Kwiatkowski DJ, et al. Identification of driver mutations in tumor specimens from 1,000 patients with lung adenocarcinoma: the NCI′s Lung Cancer Mutation Consortium (LCMC)［J］. Am Soc Clin Oncol, 2011, 29 Suppl: CRA7506. ［16］ Rosell R, Massuti Sureda B, Costa C, et al. Concomitant actionable mutations and overall survival (OS) in EGFRmutant nonsmallcell lung cancer (NSCLC) patients (p) included in the EURTAC trial: EGFR L858R, EGFR T790M, TP53 R273H and EML4ALK(V3)［J］. Ann Oncol, 2012, 23 Supple 9: abstract LBA31. ［17］ Koh Y, Kim DW, Kim TM, et al. Clinicopathologic characteristics and outcomes of patients with anaplastic lymphoma kinasepositive advanced pulmonary adenocarcinoma: suggestion for an effective screening strategy for these tumors［J］. J Thorac Oncol, 2011, 6(5): 905-912. ［18］ Paik JH, Choi CM, Kim H, et al. Clinicopathologic implication of ALK rearrangement in surgically resected lung cancer: a proposal of diagnostic algorithm for ALKrearranged adenocarcinoma［J］. Lung Cancer, 2012, 76(3): 403-409. ［19］ Blackhall F, Peters S, Kerr KM, et al. Prevalence and clinical outcomes for patients with ALK gene rearrangement in Europe: preliminary results from the European Thoracic Oncology Platform Lungscape Project［J］. Ann Oncol, 2012, 23 Supple 9: abstract 1670. ［20］ Kwak EL, Bang YJ, Camidge DR, et al. Anaplastic lymphoma kinase inhibition in nonsmallcell lung cancer［J］. N Engl J Med, 2010, 363(18): 1693-1703. ［21］ Kim DW, Ahn MJ, Shi Y, et al. Updated results of a global phase II study with crizotinib in advanced ALKpositive nonsmall cell lung cancer (NSCLC)［J］. Ann Oncol, 2012, 23 Supple 9: abstract 1230. ［22］ 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. ［23］ Camidge DR, Bang YJ, Kwak EL, et al. Activity and safety of crizotinib in patients with ALKpositive nonsmallcell lung cancer: updated results from a phase 1 study［J］. Lancet Oncol, 2012, 13(10): 1011-1019. ［24］ Doebele RC, Pilling AB, Aisner DL, et al. Mechanisms of resistance to crizotinib in patients with ALK gene rearranged nonsmall cell lung cancer［J］. Clin Cancer Res, 2012, 18(5): 1472-1482. ［25］ 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. ［26］ 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. ［27］ Shaw AT, Camidge DR, Felip E, et al. Results of firstinhuman phase I study of the ALK inhibitor LDK378 in advanced solid tumors［J］. Ann Oncol, 2012, 23 Supple 9: abstract 4400. ［28］ Gettinger S, Weiss GJ, Salgia R, et al. A firstinhuman dosefinding study of the ALK/EGFR inhibitor AP26113 in patients with advanced malignancies［J］. Ann Oncol, 2012, 23 Supple 9: abstract 4390.

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