Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
BMC Cancer
2013 May 29;13:262. doi: 10.1186/1471-2407-13-262.
Show Gene links
Show Anatomy links
Activity of EGFR-tyrosine kinase and ALK inhibitors for EML4-ALK-rearranged non-small-cell lung cancer harbored coexisting EGFR mutation.
Miyanaga A
,
Shimizu K
,
Noro R
,
Seike M
,
Kitamura K
,
Kosaihira S
,
Minegishi Y
,
Shukuya T
,
Yoshimura A
,
Kawamoto M
,
Tsuchiya S
,
Hagiwara K
,
Soda M
,
Takeuchi K
,
Yamamoto N
,
Mano H
,
Ishikawa Y
,
Gemma A
.
Abstract
BACKGROUND: The EML4-ALK (echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene) fusion oncogene represents a novel molecular target in a small subset of non-small-cell lung cancers (NSCLCs). The EML4-ALK fusion gene occurs generally in NSCLC without mutations in epidermal growth factor receptor (EGFR) and KRAS.
CASE PRESENTATION: We report that a case of EML4-ALK-positive NSCLC with EGFR mutation had a response of stable disease to both an EGFR tyrosine kinase inhibitor (EGFR-TKI) and ALK inhibitor.
CONCLUSIONS: We described the first clinical report of a patient with EML4-ALK-positive NSCLC with EGFR mutation that had a response of stable disease to both single-agent EGFR-TKI and ALK inhibitor. EML4-ALK translocation may be associated with resistance to EGFR-TKI, and EGFR signaling may contribute to resistance to ALK inhibitor in EML4-ALK-positive NSCLC.
Figure 1. Histology of the primary tumour. (A) and (B) shows a papillary adenocarcinoma (hematoxylin and eosin 200Ã magnification), (C) a mucin stain shows positive for both signet-ring and papillary morphology (PAS, 400Ã magnification). (D) immunohistochemical analysis of lung adenocarcinoma specimens with EML4-ALK fusion using a monoclonal anti-TTF-1 antibody (200Ã magnification).
Figure 2. The sequence of the junction between EML4 exon 20 and ALK exon 20.
Figure 3. Diagnosis of an EML4-ALK-positive non-small cell lung cancer. (A) Immunostaining for ALK protein expression in tumor cells. (B) The results of a break-apart FISH assay of tumor cells from a patient with rearrangement of the gene encoding ALK.
Fukuoka,
Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS).
2011, Pubmed
Fukuoka,
Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS).
2011,
Pubmed
Inamura,
EML4-ALK fusion is linked to histological characteristics in a subset of lung cancers.
2008,
Pubmed
,
Echinobase
Koivunen,
EML4-ALK fusion gene and efficacy of an ALK kinase inhibitor in lung cancer.
2008,
Pubmed
Kuo,
Good response to gefitinib in lung adenocarcinoma harboring coexisting EML4-ALK fusion gene and EGFR mutation.
2010,
Pubmed
Kwak,
Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer.
2010,
Pubmed
Lee,
Differential sensitivities to tyrosine kinase inhibitors in NSCLC harboring EGFR mutation and ALK translocation.
2012,
Pubmed
Maemondo,
Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR.
2010,
Pubmed
Mano,
Non-solid oncogenes in solid tumors: EML4-ALK fusion genes in lung cancer.
2008,
Pubmed
,
Echinobase
Mitsudomi,
Gefitinib versus cisplatin plus docetaxel in patients with non-small-cell lung cancer harbouring mutations of the epidermal growth factor receptor (WJTOG3405): an open label, randomised phase 3 trial.
2010,
Pubmed
Nagai,
Genetic heterogeneity of the epidermal growth factor receptor in non-small cell lung cancer cell lines revealed by a rapid and sensitive detection system, the peptide nucleic acid-locked nucleic acid PCR clamp.
2005,
Pubmed
Perner,
EML4-ALK fusion lung cancer: a rare acquired event.
2008,
Pubmed
Popat,
Lung adenocarcinoma with concurrent exon 19 EGFR mutation and ALK rearrangement responding to erlotinib.
2011,
Pubmed
Sasaki,
A novel ALK secondary mutation and EGFR signaling cause resistance to ALK kinase inhibitors.
2011,
Pubmed
Shaw,
Clinical features and outcome of patients with non-small-cell lung cancer who harbor EML4-ALK.
2009,
Pubmed
Shinmura,
EML4-ALK fusion transcripts, but no NPM-, TPM3-, CLTC-, ATIC-, or TFG-ALK fusion transcripts, in non-small cell lung carcinomas.
2008,
Pubmed
Soda,
Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.
2007,
Pubmed
,
Echinobase
Takeuchi,
Multiplex reverse transcription-PCR screening for EML4-ALK fusion transcripts.
2008,
Pubmed
Tanaka,
A case of lung adenocarcinoma harboring EGFR mutation and EML4-ALK fusion gene.
2012,
Pubmed
,
Echinobase
Tiseo,
EGFR and EML4-ALK gene mutations in NSCLC: a case report of erlotinib-resistant patient with both concomitant mutations.
2011,
Pubmed
Wong,
The EML4-ALK fusion gene is involved in various histologic types of lung cancers from nonsmokers with wild-type EGFR and KRAS.
2009,
Pubmed
,
Echinobase
