Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
August-2022 Volume 24 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
August-2022 Volume 24 Issue 2

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

EML4‑ALK fusion gene in non‑small cell lung cancer (Review)

  • Authors:
    • Yu Lei
    • Yan Lei
    • Xiang Shi
    • Jingjing Wang
  • View Affiliations / Copyright

    Affiliations: Department of Pathology, Qianjiang Central Hospital, Qianjiang, Hubei 433100, P.R. China, Department of Respiratory Medicine, Qianjiang Central Hospital, Qianjiang, Hubei 433100, P.R. China
    Copyright: © Lei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 277
    |
    Published online on: June 24, 2022
       https://doi.org/10.3892/ol.2022.13397
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Non‑small cell lung cancer (NSCLC) is a malignant tumor with a high morbidity and mortality rate that is a threat to human health. With the development of molecular targeted research, breakthroughs have been made on the molecular mechanism of lung cancer. The echinoderm microtubule‑associated protein‑like 4‑anaplastic lymphoma kinase (EML4‑ALK) fusion gene is one of the most important pathogenic driver genes of NSCLC discovered thus far. Four generations of targeted drugs for EML4‑ALK have been developed, with patients benefiting significantly from these drugs. Therefore, EML4‑ALK has become a research hotspot in NSCLC. The aim of the present study is to introduce the current research progress of EML4‑ALK and its association with NSCLC.
View Figures

Figure 1

Figure 2

View References

1 

Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M, Znaor A and Bray F: Cancer statistics for the year 2020: An overview. Int J Cancer. Apr 5–2021.(Epub ahead of print). View Article : Google Scholar

2 

Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, Znaor A and Bray F: Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int J Cancer. 144:1941–1953. 2019. View Article : Google Scholar : PubMed/NCBI

3 

Barta JA, Powell CA and Wisnivesky JP: Global epidemiology of lung cancer. Ann Glob Health. 85:82019. View Article : Google Scholar : PubMed/NCBI

4 

Shi J, Li D, Liang D and He Y: Epidemiology and prognosis in young lung cancer patients aged under 45 years old in northern China. Sci Rep. 11:68172021. View Article : Google Scholar : PubMed/NCBI

5 

Hamard C, Mignard X, Pecuchet N, Mathiot N, Blons H, Laurent-Puig P, Leroy K, Lupo A, Chapron J, Giraud F, et al: IHC, FISH, CISH, NGS in non-small cell lung cancer: What changes in the biomarker era? Rev Pneumol Clin. 74:327–338. 2018.(In French). View Article : Google Scholar : PubMed/NCBI

6 

Lim AS and Lim TH: Fluorescence in situ hybridization on tissue sections. Methods Mol Biol. 1541:119–125. 2017. View Article : Google Scholar : PubMed/NCBI

7 

Morganti S, Tarantino P, Ferraro E, D'Amico P, Duso BA and Curigliano G: Next generation sequencing (NGS): A revolutionary technology in pharmacogenomics and personalized medicine in cancer. Adv Exp Med Biol. 1168:9–30. 2019. View Article : Google Scholar : PubMed/NCBI

8 

Gao S, Zhang G, Lian Y, Yan L and Gao H: Exploration and analysis of the value of tumor-marker joint detection in the pathological type of lung cancer. Cell Mol Biol (Noisy-le-grand). 66:93–97. 2020. View Article : Google Scholar : PubMed/NCBI

9 

Camidge DR, Dziadziuszko R, Peters S, Mok T, Noe J, Nowicka M, Gadgeel SM, Cheema P, Pavlakis N, de Marinis F, et al: Updated efficacy and safety data and impact of the EML4-ALK fusion variant on the efficacy of alectinib in untreated ALK-positive advanced non-small cell lung cancer in the global phase III ALEX study. J Thorac Oncol. 14:1233–1243. 2019. View Article : Google Scholar : PubMed/NCBI

10 

Heigener DF and Reck M: Crizotinib. Recent Results Cancer Res. 211:57–65. 2018. View Article : Google Scholar : PubMed/NCBI

11 

Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, et al: Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature. 448:561–566. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Soda M, Takada S, Takeuchi K, Choi YL, Enomoto M, Ueno T, Haruta H, Hamada T, Yamashita Y, Ishikawa Y, et al: A mouse model for EML4-ALK-positive lung cancer. Proc Natl Acad Sci USA. 105:19893–19897. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Suprenant KA, Dean K, McKee J and Hake S: EMAP, an echinoderm microtubule-associated protein found in microtubule-ribosome complexes. J Cell Sci. 104:445–450. 1993. View Article : Google Scholar : PubMed/NCBI

14 

Fry AM, O'Regan L, Montgomery J, Adib R and Bayliss R: EML proteins in microtubule regulation and human disease. Biochem Soc Trans. 44:1281–1288. 2016. View Article : Google Scholar : PubMed/NCBI

15 

Richards MW, O'Regan L, Roth D, Montgomery JM, Straube A, Fry AM and Bayliss R: Microtubule association of EML proteins and the EML4-ALK variant 3 oncoprotein require an N-terminal trimerization domain. Biochem J. 467:529–536. 2015. View Article : Google Scholar : PubMed/NCBI

16 

Richards MW, Law EW, Rennalls LP, Busacca S, O'Regan L, Fry AM, Fennell DA and Bayliss R: Crystal structure of EML1 reveals the basis for Hsp90 dependence of oncogenic EML4-ALK by disruption of an atypical β-propeller domain. Proc Natl Acad Sci USA. 111:5195–5200. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Mano H: The EML4-ALK oncogene: Targeting an essential growth driver in human cancer. Proc Jpn Acad Ser B Phys Biol Sci. 91:193–201. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Tulpule A, Guan J, Neel DS, Allegakoen HR, Lin YP, Brown D, Chou YT, Heslin A, Chatterjee N, Perati S, et al: Kinase-mediated RAS signaling via membraneless cytoplasmic protein granules. Cell. 184:2649–2664.e18. 2021. View Article : Google Scholar : PubMed/NCBI

19 

Ladanyi M, Cavalchire G, Morris SW, Downing J and Filippa DA: Reverse transcriptase polymerase chain reaction for the Ki-1 anaplastic large cell lymphoma-associated t(2;5) translocation in Hodgkin's disease. Am J Pathol. 145:1296–1300. 1994.PubMed/NCBI

20 

Hurley SP, Clary DO, Copie V and Lefcort F: Anaplastic lymphoma kinase is dynamically expressed on subsets of motor neurons and in the peripheral nervous system. J Comp Neurol. 495:202–212. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Morris SW, Naeve C, Mathew P, James PL, Kirstein MN, Cui X and Witte DP: ALK, the chromosome 2 gene locus altered by the t(2;5) in non-Hodgkin's lymphoma, encodes a novel neural receptor tyrosine kinase that is highly related to leukocyte tyrosine kinase (LTK). Oncogene. 14:2175–2188. 1997. View Article : Google Scholar : PubMed/NCBI

22 

Golding B, Luu A, Jones R and Viloria-Petit AM: The function and therapeutic targeting of anaplastic lymphoma kinase (ALK) in non-small cell lung cancer (NSCLC). Mol Cancer. 17:522018. View Article : Google Scholar : PubMed/NCBI

23 

Hallberg B and Palmer RH: The role of the ALK receptor in cancer biology. Ann Oncol. 27 (Suppl 3):iii4–iii15. 2016. View Article : Google Scholar : PubMed/NCBI

24 

Roskoski R Jr: Anaplastic lymphoma kinase (ALK): Structure, oncogenic activation, and pharmacological inhibition. Pharmacol Res. 68:68–94. 2013. View Article : Google Scholar : PubMed/NCBI

25 

Bennasroune A, Mazot P, Boutterin MC and Vigny M: Activation of the orphan receptor tyrosine kinase ALK by zinc. Biochem Biophys Res Commun. 398:702–706. 2010. View Article : Google Scholar : PubMed/NCBI

26 

Wong DW, Leung EL, So KK, Tam IY, Sihoe AD, Cheng LC, Ho KK, Au JS, Chung LP and Pik Wong M; University of Hong Kong Lung Cancer Study Group, : The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS. Cancer. 115:1723–1733. 2009. View Article : Google Scholar : PubMed/NCBI

27 

Vašíková A: EML4-ALK fusion gene in patients with lung carcinoma: Biology, diagnostics and targeted therapy. Klin Onkol. 25:434–439. 2012.PubMed/NCBI

28 

Kodama T, Motoi N, Ninomiya H, Sakamoto H, Kitada K, Tsukaguchi T, Satoh Y, Nomura K, Nagano H, Ishii N, et al: A novel mechanism of EML4-ALK rearrangement mediated by chromothripsis in a patient-derived cell line. J Thorac Oncol. 9:1638–1646. 2014. View Article : Google Scholar : PubMed/NCBI

29 

Yang T, Liu H and Chen J: EML4-ALK fusion gene in lung cancer and its biological function. Zhongguo Fei Ai Za Zhi. 15:112–116. 2012.(In Chinese). PubMed/NCBI

30 

Bayliss R, Choi J, Fennell DA, Fry AM and Richards MW: Molecular mechanisms that underpin EML4-ALK driven cancers and their response to targeted drugs. Cell Mol Life Sci. 73:1209–1224. 2016. View Article : Google Scholar : PubMed/NCBI

31 

Robertson FM, Petricoin Iii EF, Van Laere SJ, Bertucci F, Chu K, Fernandez SV, Mu Z, Alpaugh K, Pei J, Circo R, et al: Presence of anaplastic lymphoma kinase in inflammatory breast cancer. Springerplus. 2:4972013. View Article : Google Scholar : PubMed/NCBI

32 

McQuitty E, Zhang W, Hendrickson H, Tio FO, Jagirdar J, Olsen R and Cagle PT: Lung adenocarcinoma biomarker incidence in Hispanic versus non-Hispanic white patients. Arch Pathol Lab Med. 138:390–394. 2014. View Article : Google Scholar : PubMed/NCBI

33 

Sampson J, Richards MW, Choi J, Fry AM and Bayliss R: Phase-separated foci of EML4-ALK facilitate signalling and depend upon an active kinase conformation. EMBO Rep. 22:e536932021. View Article : Google Scholar : PubMed/NCBI

34 

Li Y, Li Y, Zhang H, Shi R, Zhang Z, Liu H and Chen J: EML4-ALK-mediated activation of the JAK2-STAT pathway is critical for non-small cell lung cancer transformation. BMC Pulm Med. 21:1902021. View Article : Google Scholar : PubMed/NCBI

35 

Yang L, Li G, Zhao L, Pan F, Qiang J and Han S: Blocking the PI3K pathway enhances the efficacy of ALK-targeted therapy in EML4-ALK-positive nonsmall-cell lung cancer. Tumour Biol. 35:9759–9767. 2014. View Article : Google Scholar : PubMed/NCBI

36 

Takezawa K, Okamoto I, Nishio K, Jänne PA and Nakagawa K: Role of ERK-BIM and STAT3-survivin signaling pathways in ALK inhibitor-induced apoptosis in EML4-ALK-positive lung cancer. Clin Cancer Res. 17:2140–2148. 2011. View Article : Google Scholar : PubMed/NCBI

37 

Ducray SP, Natarajan K, Garland GD, Turner SD and Egger G: The transcriptional roles of ALK fusion proteins in tumorigenesis. Cancers (Basel). 11:10742019. View Article : Google Scholar : PubMed/NCBI

38 

Tao H, Shi L, Zhou A, Li H, Gai F, Huang Z, Che N and Liu Z: Distribution of EML4-ALK fusion variants and clinical outcomes in patients with resected non-small cell lung cancer. Lung Cancer. 149:154–161. 2020. View Article : Google Scholar : PubMed/NCBI

39 

Heuckmann JM, Balke-Want H, Malchers F, Peifer M, Sos ML, Koker M, Meder L, Lovly CM, Heukamp LC, Pao W, et al: Differential protein stability and ALK inhibitor sensitivity of EML4-ALK fusion variants. Clin Cancer Res. 18:4682–4690. 2012. View Article : Google Scholar : PubMed/NCBI

40 

Maus MK, Stephens C, Zeger G, Grimminger PP and Huang E: Identification of novel variant of EML4-ALK fusion gene in NSCLC: Potential benefits of the RT-PCR method. Int J Biomed Sci. 8:1–6. 2012.PubMed/NCBI

41 

Li T, Maus MK, Desai SJ, Beckett LA, Stephens C, Huang E, Hsiang J, Zeger G, Danenberg KD, Astrow SH and Gandara DR: Large-scale screening and molecular characterization of EML4-ALK fusion variants in archival non-small-cell lung cancer tumor specimens using quantitative reverse transcription polymerase chain reaction assays. J Thorac Oncol. 9:18–25. 2014. View Article : Google Scholar : PubMed/NCBI

42 

Cha YJ, Kim HR and Shim HS: Clinical outcomes in ALK-rearranged lung adenocarcinomas according to ALK fusion variants. J Transl Med. 14:2962016. View Article : Google Scholar : PubMed/NCBI

43 

Zhang SS, Nagasaka M, Zhu VW and Ou SI: Going beneath the tip of the iceberg. Identifying and understanding EML4-ALK variants and TP53 mutations to optimize treatment of ALK fusion positive (ALK+) NSCLC. Lung Cancer. 158:126–136. 2021. View Article : Google Scholar : PubMed/NCBI

44 

Qin Z, Sun H, Yue M, Pan X, Chen L, Feng X, Yan X, Zhu X and Ji H: Phase separation of EML4-ALK in firing downstream signaling and promoting lung tumorigenesis. Cell Discov. 7:332021. View Article : Google Scholar : PubMed/NCBI

45 

Patel M, Malhotra J and Jabbour SK: Examining EML4-ALK variants in the clinical setting: The next frontier? J Thorac Dis. 10 (Suppl 33):S4104–S4107. 2018. View Article : Google Scholar : PubMed/NCBI

46 

Schneider F and Dacic S: Histopathologic and molecular approach to staging of multiple lung nodules. Transl Lung Cancer Res. 6:540–549. 2017. View Article : Google Scholar : PubMed/NCBI

47 

Panico F, Rizzi F, Fabbri LM, Bettuzzi S and Luppi F: Clusterin (CLU) and lung cancer. Adv Cancer Res. 105:63–76. 2009. View Article : Google Scholar : PubMed/NCBI

48 

Zhang X, Wu L, Xu Y, Zhang B, Wu X, Wang Y and Pang Z: Trends in the incidence rate of lung cancer by histological type and gender in Sichuan, China, 1995–2015: A single-center retrospective study. Thorac Cancer. 9:532–541. 2018. View Article : Google Scholar : PubMed/NCBI

49 

Sasaki T, Rodig SJ, Chirieac LR and Jänne PA: The biology and treatment of EML4-ALK non-small cell lung cancer. Eur J Cancer. 46:1773–1780. 2010. View Article : Google Scholar : PubMed/NCBI

50 

Aydemirli MD, van Eendenburg JDH, van Wezel T, Oosting J, Corver WE, Kapiteijn E and Morreau H: Targeting EML4-ALK gene fusion variant 3 in thyroid cancer. Endocr Relat Cancer. 28:377–389. 2021. View Article : Google Scholar : PubMed/NCBI

51 

Akimoto E, Tokunaga M, Sato R, Yoshida A, Naito Y, Yamashita R, Kinoshita T and Kuwata T: Gastric mesenchymal tumor with smooth muscle differentiation and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion. Pathol Int. 71:707–711. 2021. View Article : Google Scholar : PubMed/NCBI

52 

Ferrara MG, Di Noia V, D'Argento E, Vita E, Damiano P, Cannella A, Ribelli M, Pilotto S, Milella M, Tortora G and Bria E: Oncogene-addicted non-small-cell lung cancer: Treatment opportunities and future perspectives. Cancers (Basel). 12:11962020. View Article : Google Scholar : PubMed/NCBI

53 

Ohba T, Toyokawa G, Osoegawa A, Hirai F, Yamaguchi M, Taguchi K, Seto T, Takenoyama M, Ichinose Y and Sugio K: Mutations of the EGFR, K-ras, EML4-ALK, and BRAF genes in resected pathological stage I lung adenocarcinoma. Surg Today. 46:1091–1098. 2016. View Article : Google Scholar : PubMed/NCBI

54 

Guo Y, Ma J, Lyu X, Liu H, Wei B, Zhao J, Fu S, Ding L and Zhang J: Non-small cell lung cancer with EML4-ALK translocation in Chinese male never-smokers is characterized with early-onset. BMC Cancer. 14:8342014. View Article : Google Scholar : PubMed/NCBI

55 

Lin C, Shi X, Yang S, Zhao J, He Q, Jin Y and Yu X: Comparison of ALK detection by FISH, IHC and NGS to predict benefit from crizotinib in advanced non-small-cell lung cancer. Lung Cancer. 131:62–68. 2019. View Article : Google Scholar : PubMed/NCBI

56 

Teixidó C, Karachaliou N, Peg V, Gimenez-Capitan A and Rosell R: Concordance of IHC, FISH and RT-PCR for EML4-ALK rearrangements. Transl Lung Cancer Res. 3:70–74. 2014.PubMed/NCBI

57 

Pekar-Zlotin M, Hirsch FR, Soussan-Gutman L, Ilouze M, Dvir A, Boyle T, Wynes M, Miller VA, Lipson D, Palmer GA, et al: Fluorescence in situ hybridization, immunohistochemistry, and next-generation sequencing for detection of EML4-ALK rearrangement in lung cancer. Oncologist. 20:316–322. 2015. View Article : Google Scholar : PubMed/NCBI

58 

Bayani J and Squire JA: Fluorescence in situ hybridization (FISH). Curr Protoc Cell Biol. Chapter 22: Unit 22.4. 2004. View Article : Google Scholar

59 

Querido E, Dekakra-Bellili L and Chartrand P: RNA fluorescence in situ hybridization for high-content screening. Methods. 126:149–155. 2017. View Article : Google Scholar : PubMed/NCBI

60 

Liu L, Zhan P, Zhou X, Song Y, Zhou X, Yu L and Wang J: Detection of EML4-ALK in lung adenocarcinoma using pleural effusion with FISH, IHC, and RT-PCR methods. PLoS One. 10:e01170322015. View Article : Google Scholar : PubMed/NCBI

61 

Wang Y, Zhang J, Gao G, Li X, Zhao C, He Y, Su C, Zhang S, Chen X, Zhang J, et al: EML4-ALK fusion detected by RT-PCR confers similar response to crizotinib as detected by FISH in patients with advanced non-small-cell lung cancer. J Thorac Oncol. 10:1546–1552. 2015. View Article : Google Scholar : PubMed/NCBI

62 

Behjati S and Tarpey PS: What is next generation sequencing? Arch Dis Child Educ Pract Ed. 98:236–238. 2013. View Article : Google Scholar : PubMed/NCBI

63 

Hume S, Nelson TN, Speevak M, McCready E, Agatep R, Feilotter H, Parboosingh J, Stavropoulos DJ, Taylor S and Stockley TL; Canadian College of Medical Geneticists (CCMG), : CCMG practice guideline: Laboratory guidelines for next-generation sequencing. J Med Genet. 56:792–800. 2019. View Article : Google Scholar : PubMed/NCBI

64 

Jennings LJ, Arcila ME, Corless C, Kamel-Reid S, Lubin IM, Pfeifer J, Temple-Smolkin RL, Voelkerding KV and Nikiforova MN: Guidelines for validation of next-generation sequencing-based oncology panels: A joint consensus recommendation of the association for molecular pathology and college of American pathologists. J Mol Diagn. 19:341–365. 2017. View Article : Google Scholar : PubMed/NCBI

65 

Ma PC: Personalized targeted therapy in advanced non-small cell lung cancer. Cleve Clin J Med. 79 (Electronic Suppl 1):eS56–eS60. 2012. View Article : Google Scholar : PubMed/NCBI

66 

Fallet V, Toper C, Antoine M, Cadranel J and Wislez M: Management of crizotinib, a new individualized treatment. Bull Cancer. 99:787–791. 2012.(In French). View Article : Google Scholar : PubMed/NCBI

67 

Khan M, Lin J, Liao G, Tian Y, Liang Y, Li R, Liu M and Yuan Y: ALK inhibitors in the treatment of ALK positive NSCLC. Front Oncol. 8:5572019. View Article : Google Scholar : PubMed/NCBI

68 

Cameron LB, Hitchen N, Chandran E, Morris T, Manser R, Solomon BJ and Jordan V: Targeted therapy for advanced anaplastic lymphoma kinase (<I>ALK</I>)-rearranged non-small cell lung cancer. Cochrane Database Syst Rev. 1:CD0134532022.PubMed/NCBI

69 

Zhu Q, Hu H, Jiang F, Guo CY, Yang XW, Liu X and Kuang YK: Meta-analysis of incidence and risk of severe adverse events and fatal adverse events with crizotinib monotherapy in patients with ALK-positive NSCLC. Oncotarget. 8:75372–75380. 2017. View Article : Google Scholar : PubMed/NCBI

70 

Solomon BJ, Mok T, Kim DW, Wu YL, Nakagawa K, Mekhail T, Felip E, Cappuzzo F, Paolini J, Usari T, et al: First-line crizotinib versus chemotherapy in ALK-positive lung cancer. N Engl J Med. 371:2167–2177. 2014. View Article : Google Scholar : PubMed/NCBI

71 

Casaluce F, Sgambato A, Sacco PC, Palazzolo G, Maione P, Rossi A, Ciardiello F and Gridelli C: Resistance to crizotinib in advanced non-small cell lung cancer (NSCLC) with ALK rearrangement: Mechanisms, treatment strategies and new targeted therapies. Curr Clin Pharmacol. 11:77–87. 2016. View Article : Google Scholar : PubMed/NCBI

72 

Dhillon S and Clark M: Ceritinib: First global approval. Drugs. 74:1285–1291. 2014. View Article : Google Scholar : PubMed/NCBI

73 

Spencer SA, Riley AC, Matthew A and Di Pasqua AJ: Brigatinib: Novel ALK inhibitor for non-small-cell lung cancer. Ann Pharmacother. 53:621–626. 2019. View Article : Google Scholar : PubMed/NCBI

74 

Herden M and Waller CF: Alectinib. Recent Results Cancer Res. 211:247–256. 2018. View Article : Google Scholar : PubMed/NCBI

75 

Shaw AT, Solomon BJ, Besse B, Bauer TM, Lin CC, Soo RA, Riely GJ, Ou SI, Clancy JS, Li S, et al: ALK resistance mutations and efficacy of lorlatinib in advanced anaplastic lymphoma kinase-positive non-small-cell lung cancer. J Clin Oncol. 37:1370–1379. 2019. View Article : Google Scholar : PubMed/NCBI

76 

Yun MR, Kim DH, Kim SY, Joo HS, Lee YW, Choi HM, Park CW, Heo SG, Kang HN, Lee SS, et al: Repotrectinib exhibits potent antitumor activity in treatment-naïve and solvent-front-mutant ROS1-rearranged non-small cell lung cancer. Clin Cancer Res. 26:3287–3295. 2020. View Article : Google Scholar : PubMed/NCBI

77 

Drilon A, Ou SI, Cho BC, Kim DW, Lee J, Lin JJ, Zhu VW, Ahn MJ, Camidge DR, Nguyen J, et al: Repotrectinib (TPX-0005) is a next-generation ROS1/TRK/ALK inhibitor that potently inhibits ROS1/TRK/ALK solvent-front mutations. Cancer Discov. 8:1227–1236. 2018. View Article : Google Scholar : PubMed/NCBI

78 

Revannasiddaiah S, Thakur P, Bhardwaj B, Susheela SP and Madabhavi I: Pulmonary adenocarcinoma: Implications of the recent advances in molecular biology, treatment and the IASLC/ATS/ERS classification. J Thorac Dis. 6 (Suppl 5):S502–S525. 2014.PubMed/NCBI

79 

Lu Z, Wang X, Luo Y, Wei J, Zeng Z, Xiong Q, Cai J and Liu A: EGFR (p. G719A+L747V)/EML4-ALK co-alterations in lung adenocarcinoma with leptomeningeal metastasis responding to afatinib treatment: A case report. Onco Targets Ther. 14:2823–2828. 2021. View Article : Google Scholar : PubMed/NCBI

80 

Rybarczyk-Kasiuchnicz A, Ramlau R and Stencel K: Treatment of brain metastases of non-small cell lung carcinoma. Int J Mol Sci. 22:5932021. View Article : Google Scholar : PubMed/NCBI

81 

Okada K, Araki M, Sakashita T, Ma B, Kanada R, Yanagitani N, Horiike A, Koike S, Oh-Hara T, Watanabe K, et al: Prediction of ALK mutations mediating ALK-TKIs resistance and drug re-purposing to overcome the resistance. EBioMedicine. 41:105–119. 2019. View Article : Google Scholar : PubMed/NCBI

82 

Lin JJ, Zhu VW, Yoda S, Yeap BY, Schrock AB, Dagogo-Jack I, Jessop NA, Jiang GY, Le LP, Gowen K, et al: Impact of EML4-ALK variant on resistance mechanisms and clinical outcomes in ALK-positive lung cancer. J Clin Oncol. 36:1199–1206. 2018. View Article : Google Scholar : PubMed/NCBI

83 

Dagogo-Jack I and Shaw AT: Crizotinib resistance: Implications for therapeutic strategies. Ann Oncol. 27 (Suppl 3):iii42–iii50. 2016. View Article : Google Scholar : PubMed/NCBI

84 

Katayama R, Shaw AT, Khan TM, Mino-Kenudson M, Solomon BJ, Halmos B, Jessop NA, Wain JC, Yeo AT, Benes C, et al: Mechanisms of acquired crizotinib resistance in ALK-rearranged lung Cancers. Sci Transl Med. 4:120ra172012. View Article : Google Scholar : PubMed/NCBI

85 

Kunimasa K, Hirotsu Y, Kukita Y, Ueda Y, Sato Y, Kimura M, Otsuka T, Hamamoto Y, Tamiya M, Inoue T, et al: EML4-ALK fusion variant.3 and co-occurrent PIK3CA E542K mutation exhibiting primary resistance to three generations of ALK inhibitors. Cancer Genet. 256–257. 131–135. 2021.

86 

Kwon JH, Kim KJ, Sung JH, Suh KJ, Lee JY, Kim JW, Kim SH, Lee JO, Kim JW, Kim YJ, et al: Afatinib overcomes pemetrexed-acquired resistance in non-small cell lung cancer cells harboring an EML4-ALK rearrangement. Cells. 8:15382019. View Article : Google Scholar : PubMed/NCBI

87 

Mittal V: Epithelial mesenchymal transition in tumor metastasis. Annu Rev Pathol. 13:395–412. 2018. View Article : Google Scholar : PubMed/NCBI

88 

Shen J, Meng Y, Wang K, Gao M, Du J, Wang J, Li Z, Zuo D and Wu Y: EML4-ALK G1202R mutation induces EMT and confers resistance to ceritinib in NSCLC cells via activation of STAT3/Slug signaling. Cell Signal. 92:1102642022. View Article : Google Scholar : PubMed/NCBI

89 

Guo F, Liu X, Qing Q, Sang Y, Feng C, Li X, Jiang L, Su P and Wang Y: EML4-ALK induces epithelial-mesenchymal transition consistent with cancer stem cell properties in H1299 non-small cell lung cancer cells. Biochem Biophys Res Commun. 459:398–404. 2015. View Article : Google Scholar : PubMed/NCBI

90 

Voena C, Varesio LM, Zhang L, Menotti M, Poggio T, Panizza E, Wang Q, Minero VG, Fagoonee S, Compagno M, et al: Oncogenic ALK regulates EMT in non-small cell lung carcinoma through repression of the epithelial splicing regulatory protein 1. Oncotarget. 7:33316–33330. 2016. View Article : Google Scholar : PubMed/NCBI

91 

De Mello RA, Liu DJ, Aguiar PN and Tadokoro H: EGFR and EML4-ALK updated therapies in non-small cell lung cancer. Recent Pat Anticancer Drug Discov. 11:393–400. 2016. View Article : Google Scholar : PubMed/NCBI

92 

Guo J, Shi J, Yao M, Jin Y, Liu D, Liu W, Wang K and Jiang D: A rare double ALK fusion variant EML4-ALK and CDK15-ALK in lung adenocarcinoma and response to crizotinib: A case report. Medicine (Baltimore). 99:e226312020. View Article : Google Scholar : PubMed/NCBI

93 

Laszlo A, Thotala D and Hallahan DE: Membrane phospholipids, EML4-ALK, and Hsp90 as novel targets in lung cancer treatment. Cancer J. 19:238–246. 2013. View Article : Google Scholar : PubMed/NCBI

94 

Gelatti ACZ, Drilon A and Santini FC: Optimizing the sequencing of tyrosine kinase inhibitors (TKIs) in epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC). Lung Cancer. 137:113–122. 2019. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Lei Y, Lei Y, Shi X and Wang J: EML4‑ALK fusion gene in non‑small cell lung cancer (Review). Oncol Lett 24: 277, 2022.
APA
Lei, Y., Lei, Y., Shi, X., & Wang, J. (2022). EML4‑ALK fusion gene in non‑small cell lung cancer (Review). Oncology Letters, 24, 277. https://doi.org/10.3892/ol.2022.13397
MLA
Lei, Y., Lei, Y., Shi, X., Wang, J."EML4‑ALK fusion gene in non‑small cell lung cancer (Review)". Oncology Letters 24.2 (2022): 277.
Chicago
Lei, Y., Lei, Y., Shi, X., Wang, J."EML4‑ALK fusion gene in non‑small cell lung cancer (Review)". Oncology Letters 24, no. 2 (2022): 277. https://doi.org/10.3892/ol.2022.13397
Copy and paste a formatted citation
x
Spandidos Publications style
Lei Y, Lei Y, Shi X and Wang J: EML4‑ALK fusion gene in non‑small cell lung cancer (Review). Oncol Lett 24: 277, 2022.
APA
Lei, Y., Lei, Y., Shi, X., & Wang, J. (2022). EML4‑ALK fusion gene in non‑small cell lung cancer (Review). Oncology Letters, 24, 277. https://doi.org/10.3892/ol.2022.13397
MLA
Lei, Y., Lei, Y., Shi, X., Wang, J."EML4‑ALK fusion gene in non‑small cell lung cancer (Review)". Oncology Letters 24.2 (2022): 277.
Chicago
Lei, Y., Lei, Y., Shi, X., Wang, J."EML4‑ALK fusion gene in non‑small cell lung cancer (Review)". Oncology Letters 24, no. 2 (2022): 277. https://doi.org/10.3892/ol.2022.13397
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team