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      ALK融合基因阳性非小细胞肺癌的研究进展 Translated title: Current Status for Anaplastic Lymphoma Kinase in Non-small Cell Lung Cancer

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          Abstract

          ALK基因重排在非小细胞肺癌(non-small cell lung cancer, NSCLC)中发生率约3%-5%。 ALK基因抑制剂近年来取得极大突破,明显延长了ALK阳新晚期NSCLC患者的生存期;但大部分患者持续用药后会出现获得性耐药。本文分别从 ALK基因背景、检测方法、三代ALK抑制剂的治疗效果以及耐药后的策略、展望进行了阐述。希望对临床工作有参考价值和借鉴意义。

          Translated abstract

          The incidence of ALK gene rearrangement in non-small cell lung cancer (NSCLC) was about 3% to 5%. ALK gene inhibitors have made great breakthrough in recent years, significantly extending the survival period of patients with ALK(+) advanced NSCLC. But the majority of patients will be acquired drug resistance after treatment. This article has been explained separately from the ALK genetic background, the detection method, the treatment of the three generations of ALK inhibitors and the strategy after drug resistance. It is desire to have reference value and reference meaning for clinical work.

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          Most cited references37

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          Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK.

          The EML4-ALK fusion oncogene represents a novel molecular target in a small subset of non-small-cell lung cancers (NSCLC). To aid in identification and treatment of these patients, we examined the clinical characteristics and treatment outcomes of patients who had NSCLC with and without EML4-ALK. Patients with NSCLC were selected for genetic screening on the basis of two or more of the following characteristics: female sex, Asian ethnicity, never/light smoking history, and adenocarcinoma histology. EML4-ALK was identified by using fluorescent in situ hybridization for ALK rearrangements and was confirmed by immunohistochemistry for ALK expression. EGFR and KRAS mutations were determined by DNA sequencing. Of 141 tumors screened, 19 (13%) were EML4-ALK mutant, 31 (22%) were EGFR mutant, and 91 (65%) were wild type (WT/WT) for both ALK and EGFR. Compared with the EGFR mutant and WT/WT cohorts, patients with EML4-ALK mutant tumors were significantly younger (P < .001 and P = .005) and were more likely to be men (P = .036 and P = .039). Patients with EML4-ALK-positive tumors, like patients who harbored EGFR mutations, also were more likely to be never/light smokers compared with patients in the WT/WT cohort (P < .001). Eighteen of the 19 EML4-ALK tumors were adenocarcinomas, predominantly the signet ring cell subtype. Among patients with metastatic disease, EML4-ALK positivity was associated with resistance to EGFR tyrosine kinase inhibitors (TKIs). Patients in the EML4-ALK cohort and the WT/WT cohort showed similar response rates to platinum-based combination chemotherapy and no difference in overall survival. EML4-ALK defines a molecular subset of NSCLC with distinct clinical characteristics. Patients who harbor this mutation do not benefit from EGFR TKIs and should be directed to trials of ALK-targeted agents.
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            First-line ceritinib versus platinum-based chemotherapy in advanced ALK -rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study

            The efficacy of ceritinib in patients with untreated anaplastic lymphoma kinase (ALK)-rearranged non-small-cell lung cancer (NSCLC) is not known. We assessed the efficacy and safety of ceritinib versus platinum-based chemotherapy in these patients.
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              Alectinib versus crizotinib in patients with ALK-positive non-small-cell lung cancer (J-ALEX): an open-label, randomised phase 3 trial.

              Alectinib, a potent, highly selective, CNS-active inhibitor of anaplastic lymphoma kinase (ALK), showed promising efficacy and tolerability in the single-arm phase 1/2 AF-001JP trial in Japanese patients with ALK-positive non-small-cell lung cancer. Given those promising results, we did a phase 3 trial to directly compare the efficacy and safety of alectinib and crizotinib.
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                Author and article information

                Contributors
                Journal
                Zhongguo Fei Ai Za Zhi
                Zhongguo Fei Ai Za Zhi
                ZGFAZZ
                Chinese Journal of Lung Cancer
                中国肺癌杂志编辑部 (天津市和平区南京路228号300020 )
                1009-3419
                1999-6187
                20 September 2018
                : 21
                : 9
                : 703-711
                Affiliations
                [ ] 100730 北京,中国医学科学院 北京协和医学院北京协和医院呼吸内科 Department of Respiratory Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing 100730, China
                Author notes
                张力, Li ZHANG, E-mail: zhanglipumch@ 123456aliyun.com
                Article
                zgfazz-21-9-703
                10.3779/j.issn.1009-3419.2018.09.10
                6136995
                30201071
                25a281e6-880a-43c0-86f6-18505b38d457
                版权所有©《中国肺癌杂志》编辑部2018Copyright ©2018 Chinese Journal of Lung Cancer. All rights reserved.

                This is an open access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY 3.0) License. See: https://creativecommons.org/licenses/by/3.0/

                History
                : 16 March 2018
                : 15 April 2018
                : 26 April 2018
                Categories
                综述

                alk融合基因,nsclc,alk抑制剂,耐药,检测方法,alk gene,alk-tki,drug resistance,detection method

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