Home LiteratureArticle Details
PMID: 20418096 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Review

The biology and treatment of EML4-ALK non-small cell lung cancer.

European journal of cancer (Oxford, England : 1990) ·Vol. 46 ·No. 10 ·2010-07-00 ·Pages 1773-80

Sasaki T, Rodig SJ, Chirieac LR, Jänne PA

Abstract

The fusion between echinoderm microtubule-associated protein-like 4 (EML4) and anaplastic lymphoma kinase (ALK) has recently been identified in a subset of non-small cell lung cancers (NSCLCs). EML4-ALK is most often detected in never smokers with lung cancer and has unique pathologic features. EML4-ALK is oncogenic both in vitro and in vivo and ALK kinase inhibitors are quite effective in pre-clinical model systems. More recently ALK inhibitors have entered clinical development and remarkably clinical efficacy has been observed in NSCLC patients harbouring EML4-ALK translocations. This review will focus on the biology, clinical characteristics, diagnosis and treatment of EML4-ALK NSCLC.

MeSH Terms
Anaplastic Lymphoma Kinase Antineoplastic Agents/therapeutic use Carcinoma, Non-Small-Cell Lung/diagnosis,genetics,therapy Enzyme Inhibitors/therapeutic use Gene Rearrangement Humans In Situ Hybridization, Fluorescence Lung Neoplasms/diagnosis,genetics,therapy Mutation Oncogene Proteins, Fusion/genetics Protein-Tyrosine Kinases/antagonists & inhibitors Receptor Protein-Tyrosine Kinases Reverse Transcriptase Polymerase Chain Reaction Smoking/genetics Translocation, Genetic
Chemicals
Antineoplastic Agents EML4-ALK fusion protein, human Enzyme Inhibitors Oncogene Proteins, Fusion ALK protein, human Anaplastic Lymphoma Kinase Protein-Tyrosine Kinases Receptor Protein-Tyrosine Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Sasaki Takaaki
Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Rodig Scott J
Chirieac Lucian R
Jänne Pasi A
References (42)
42 references, click to expand
  1. EML4-ALK fusion lung cancer: a rare acquired event.
    Neoplasia. 2008 Mar;10(3):298-302 PMID: 18320074
  2. Genomic alterations of anaplastic lymphoma kinase may sensitize tumors to anaplastic lymphoma kinase inhibitors.
    Cancer Res. 2008 May 1;68(9):3389-95 PMID: 18451166
  3. Cigarette smoking is strongly associated with mutation of the K-ras gene in patients with primary adenocarcinoma of the lung.
    Cancer. 2001 Sep 15;92(6):1525-30 PMID: 11745231
  4. TP53 and KRAS mutation load and types in lung cancers in relation to tobacco smoke: distinct patterns in never, former, and current smokers.
    Cancer Res. 2005 Jun 15;65(12):5076-83 PMID: 15958551
  5. Clinicopathologic significance of the mutations of the epidermal growth factor receptor gene in patients with non-small cell lung cancer.
    Clin Cancer Res. 2005 Oct 1;11(19 Pt 1):6816-22 PMID: 16203769
  6. EML4-ALK fusion transcript is not found in gastrointestinal and breast cancers.
    Br J Cancer. 2008 May 6;98(9):1536-9 PMID: 18414414
  7. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer.
    N Engl J Med. 2002 Jan 10;346(2):92-8 PMID: 11784875
  8. The global burden of cancer: priorities for prevention.
    Carcinogenesis. 2010 Jan;31(1):100-10 PMID: 19934210
  9. TRK-fused gene (TFG) is a new partner of ALK in anaplastic large cell lymphoma producing two structurally different TFG-ALK translocations.
    Blood. 1999 Nov 1;94(9):3265-8 PMID: 10556217
  10. Gefitinib induces apoptosis in the EGFRL858R non-small-cell lung cancer cell line H3255.
    Cancer Res. 2004 Oct 15;64(20):7241-4 PMID: 15492241
  11. Detection of t(2;5) in anaplastic large cell lymphoma: comparison of immunohistochemical studies, FISH, and RT-PCR in paraffin-embedded tissue.
    Am J Surg Pathol. 1999 Nov;23(11):1386-92 PMID: 10555007
  12. Epidermal growth factor receptor mutations in needle biopsy/aspiration samples predict response to gefitinib therapy and survival of patients with advanced nonsmall cell lung cancer.
    Int J Cancer. 2006 Feb 15;118(4):963-9 PMID: 16152581
  13. Mutations in the LKB1 tumour suppressor are frequently detected in tumours from Caucasian but not Asian lung cancer patients.
    Br J Cancer. 2008 Jul 22;99(2):245-52 PMID: 18594528
  14. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma.
    N Engl J Med. 2009 Sep 3;361(10):947-57 PMID: 19692680
  15. A novel, highly sensitive antibody allows for the routine detection of ALK-rearranged lung adenocarcinomas by standard immunohistochemistry.
    Clin Cancer Res. 2010 Mar 1;16(5):1561-71 PMID: 20179225
  16. The Nf2 tumor suppressor, merlin, functions in Rac-dependent signaling.
    Dev Cell. 2001 Jul;1(1):63-72 PMID: 11703924
  17. Biomarkers of response to epidermal growth factor receptor inhibitors in Non-Small-Cell Lung Cancer Working Group: standardization for use in the clinical trial setting.
    J Clin Oncol. 2008 Feb 20;26(6):983-94 PMID: 18281673
  18. Exon array profiling detects EML4-ALK fusion in breast, colorectal, and non-small cell lung cancers.
    Mol Cancer Res. 2009 Sep;7(9):1466-76 PMID: 19737969
  19. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer.
    Cell. 2007 Dec 14;131(6):1190-203 PMID: 18083107
  20. Epidermal growth factor receptor mutation in lung cancer are linked to bronchioloalveolar differentiation.
    Am J Surg Pathol. 2006 Oct;30(10):1309-15 PMID: 17001163
  21. EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer.
    Clin Cancer Res. 2008 Jul 1;14(13):4275-83 PMID: 18594010
  22. EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers.
    J Thorac Oncol. 2008 Jan;3(1):13-7 PMID: 18166835
  23. Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK.
    J Clin Oncol. 2009 Sep 10;27(26):4247-53 PMID: 19667264
  24. Distinct epidermal growth factor receptor and KRAS mutation patterns in non-small cell lung cancer patients with different tobacco exposure and clinicopathologic features.
    Clin Cancer Res. 2006 Mar 1;12(5):1647-53 PMID: 16533793
  25. Somatic mutations of the HER2 kinase domain in lung adenocarcinomas.
    Cancer Res. 2005 Mar 1;65(5):1642-6 PMID: 15753357
  26. EML4-ALK rearrangement in non-small cell lung cancer and non-tumor lung tissues.
    Am J Pathol. 2009 Feb;174(2):661-70 PMID: 19147828
  27. Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma.
    Mol Cancer Ther. 2007 Dec;6(12 Pt 1):3314-22 PMID: 18089725
  28. Clinicopathologic features of non-small-cell lung cancer with EML4-ALK fusion gene.
    Ann Surg Oncol. 2010 Mar;17(3):889-97 PMID: 20183914
  29. Identification of novel isoforms of the EML4-ALK transforming gene in non-small cell lung cancer.
    Cancer Res. 2008 Jul 1;68(13):4971-6 PMID: 18593892
  30. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.
    Nature. 2007 Aug 2;448(7153):561-6 PMID: 17625570
  31. Unique clinicopathologic features characterize ALK-rearranged lung adenocarcinoma in the western population.
    Clin Cancer Res. 2009 Aug 15;15(16):5216-23 PMID: 19671850
  32. EML4-ALK lung cancers are characterized by rare other mutations, a TTF-1 cell lineage, an acinar histology, and young onset.
    Mod Pathol. 2009 Apr;22(4):508-15 PMID: 19234440
  33. Patterns of EGFR, HER2, TP53, and KRAS mutations of p14arf expression in non-small cell lung cancers in relation to smoking history.
    Cancer Res. 2007 Jun 15;67(12):5667-72 PMID: 17575133
  34. KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer.
    Clin Cancer Res. 2009 May 1;15(9):3143-9 PMID: 19383809
  35. EML4-ALK fusion transcripts, but no NPM-, TPM3-, CLTC-, ATIC-, or TFG-ALK fusion transcripts, in non-small cell lung carcinomas.
    Lung Cancer. 2008 Aug;61(2):163-9 PMID: 18242762
  36. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers.
    J Natl Cancer Inst. 2005 Mar 2;97(5):339-46 PMID: 15741570
  37. A mouse model for EML4-ALK-positive lung cancer.
    Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19893-7 PMID: 19064915
  38. Multiplex reverse transcription-PCR screening for EML4-ALK fusion transcripts.
    Clin Cancer Res. 2008 Oct 15;14(20):6618-24 PMID: 18927303
  39. The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS.
    Cancer. 2009 Apr 15;115(8):1723-33 PMID: 19170230
  40. Female sex and bronchioloalveolar pathologic subtype predict EGFR mutations in non-small cell lung cancer.
    Chest. 2005 Jul;128(1):317-21 PMID: 16002952
  41. The relationship between epidermal growth factor receptor mutations and clinicopathologic features in non-small cell lung cancers.
    Clin Cancer Res. 2005 Feb 1;11(3):1167-73 PMID: 15709185
  42. Lung cancer in never smokers--a different disease.
    Nat Rev Cancer. 2007 Oct;7(10):778-90 PMID: 17882278
Article Info
Journal
European journal of cancer (Oxford, England : 1990)
Abbr.
Eur J Cancer
ISSN
1879-0852
DOI
10.1016/j.ejca.2010.04.002
Published
2010-07-00
Epub
2010-00-24
Pages
1773-80
Language
English
Region
England
NLM ID
9005373
PMCID
PMC2888755
Subset
IM
Grants
NCI NIH HHS · R01 CA136851 · United States
NCI NIH HHS · R01 CA136851-02 · United States
NCI NIH HHS · R01CA136851 · United States
External Links
PubMed source DOI: 10.1016/j.ejca.2010.04.002 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2