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Cited by 993

The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.

EML4-ALK Fusion Gene and Efficacy of an ALK Kinase Inhibitor in Lung Cancer

Open access
Koivunen, Jussi P., Mermel, Craig, Zejnullahu, Kreshnik, Murphy, Carly, Lifshits, Eugene, Holmes, Alison J., Choi, Hwan Geun, Kim, Jhingook, Chiang, Derek, Thomas, Roman, Lee, Jinseon, Richards, William G., Sugarbaker, David J., Ducko, Christopher, Lindeman, Neal, Marcoux, J. Paul, Engelman, Jeffrey A., Gray, Nathanael S., Lee, Charles, Meyerson, Matthew, Jänne, Pasi A.·2008·Clinical Cancer Research

Abstract

Purpose: The EML4-ALK fusion gene has been detected in ∼7% of Japanese non-small cell lung cancers (NSCLC). We determined the frequency of EML4-ALK in Caucasian NSCLC and in NSCLC cell lines. We also determined whether TAE684, a specific ALK kinase inhibitor, would inhibit the growth of EML4-ALK-containing cell lines in vitro and in vivo. Experimental Design: We screened 305 primary NSCLC [both U.S. (n = 138) and Korean (n = 167) patients] and 83 NSCLC cell lines using reverse transcription-PCR and by exon array analyses. We evaluated the efficacy of TAE684 against NSCLC cell lines in vitro and in vivo. Results: We detected four different variants, including two novel variants, of EML4-ALK using reverse transcription-PCR in 8 of 305 tumors (3%) and 3 of 83 (3.6%) NSCLC cell lines. All EML4-ALK-containing tumors and cell lines were adenocarcinomas. EML4-ALK was detected more frequently in NSCLC patients who were never or light (<10 pack-years) cigarette smokers compared with current/former smokers (6% versus 1%; P = 0.049). TAE684 inhibited the growth of one of three (H3122) EML4-ALK-containing cell lines in vitro and in vivo, inhibited Akt phosphorylation, and caused apoptosis. In another EML4-ALK cell line, DFCI032, TAE684 was ineffective due to coactivation of epidermal growth factor receptor and ERBB2. The combination of TAE684 and CL-387,785 (epidermal growth factor receptor/ERBB2 kinase inhibitor) inhibited growth and Akt phosphorylation and led to apoptosis in the DFCI032 cell line. Conclusions: EML4-ALK is found in the minority of NSCLC. ALK kinase inhibitors alone or in combination may nevertheless be clinically effective treatments for NSCLC patients whose tumors contain EML4-ALK.

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Metadata

Authors
Koivunen, J. P., Mermel, C., Zejnullahu, K., Murphy, C., Lifshits, E., Holmes, A. J., Choi, H. G., Kim, J., Chiang, D., Thomas, R., Lee, J., Richards, W. G., Sugarbaker, D. J., Ducko, C., Lindeman, N., Marcoux, J. P., Engelman, J. A., Gray, N. S., Lee, C., Meyerson, M., & Jänne, P. A.
Venue
Clinical Cancer Research
Published
2008-07-01
Volume
14
Issue
13
Pages
4275-4283
ISSN
  • 1078-0432 (ISSN-L)
  • 1557-3265
OpenAlex
W2168106545
Cited by
993
References
5
FWCI
46.47
Type
journal article
Language
en
Open access
green

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The paper
Koivunen, J. P., Mermel, C., Zejnullahu, K., Murphy, C., Lifshits, E., Holmes, A. J., Choi, H. G., Kim, J., Chiang, D., Thomas, R., Lee, J., Richards, W. G., Sugarbaker, D. J., Ducko, C., Lindeman, N., Marcoux, J. P., Engelman, J. A., Gray, N. S., Lee, C., . . . Jänne, P. A. (2008). EML4-ALK Fusion Gene and Efficacy of an ALK Kinase Inhibitor in Lung Cancer. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.ccr-08-0168

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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.