EML4-ALK positive lung cancer
EML4-ALK positive lung cancer is a medical term that refers to a primary malignant lung tumor whose cells contain a characteristic abnormal configuration of DNA wherein the echinoderm microtubule-associated protein-like 4 (EML4) gene is fused to the anaplastic lymphoma kinase (ALK) gene. This abnormal gene fusion leads to the production of a protein (EML4-ALK) that appears, in many cases, to promote and maintain the malignant behavior of the cancer cells.[1]
The transforming EML4-ALK fusion gene was first reported in non-small cell lung carcinoma (NSCLC) in 2007.[2]
Classification
Most lung carcinomas containing the EML4-ALK gene fusion are adenocarcinomas.
Some studies suggest that the papillary adenocarcinoma and the signet ring cell adenocarcinoma[3] variants are more likely to carry this fused gene than other histological variants.
Epidemiology
EML4-ALK gene fusions occur almost exclusively in carcinomas arising in non-smokers.[4] About 4% of non-small-cell lung carcinomas involve an EML4-ALK tyrosine kinase fusion gene.[5] 4–6% of lung adenocarcinomas involve the fusion gene.[6]
EML4-ALK mutation rarely occurs in combination with K-RAS or EGFR mutations.
Signs and symptoms
The signs and symptoms of this lung cancer variant seem to mimic those of the underlying major cell type.
Diagnosis
See screening below.[7]
There is a companion diagnostic to detect the EML4-ALK fusion protein.
Screening
A 2011 consensus recommendation from 37 Canadian lung cancer specialists found that, as of June 2011, there was insufficient evidence to recommend routine screening of lung cancer specimens for EML4-ALK fusions, but that may soon change.[7]
Treatment
Crizotinib is a targeted therapy (FDA approved in 2011) that targets the EML4/ALK fusion gene.
Alectinib was approved (for this) by Japan in 2014[8] and by US FDA in 2015.[9]
Prognosis
Treatment with crizotinib achieves 60% response rate.[6]
References
- ↑ Soda M, Choi YL, Enomoto M, et al. (August 2007). "Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer". Nature. 448 (7153): 561–6. doi:10.1038/nature05945. PMID 17625570.
- ↑ Sasaki T, Rodig SJ, Chirieac LR, Jänne PA (July 2010). "The biology and treatment of EML4-ALK non-small cell lung cancer". Eur. J. Cancer. 46 (10): 1773–80. doi:10.1016/j.ejca.2010.04.002. PMC 2888755
. PMID 20418096. - ↑ Koh Y, Kim DW, Kim TM, et al. (May 2011). "Clinicopathologic characteristics and outcomes of patients with anaplastic lymphoma kinase-positive advanced pulmonary adenocarcinoma: suggestion for an effective screening strategy for these tumors". J Thorac Oncol. 6 (5): 905–12. doi:10.1097/JTO.0b013e3182111461. PMID 21358343.
- ↑ Martelli MP, Sozzi G, Hernandez L, et al. (February 2009). "EML4-ALK rearrangement in non-small cell lung cancer and non-tumor lung tissues". Am. J. Pathol. 174 (2): 661–70. doi:10.2353/ajpath.2009.080755. PMC 2630573. PMID 19147828.
- ↑ Kumar, V; Abbas AK; Aster JC (2013). "Chapter 5". Robbins Basic Pathology (9th ed.). Elsevier Saunders. p. 212. ISBN 978-1-4377-1781-5.
- 1 2 Bayliss, R; Choi, J (March 2016). "Molecular mechanisms that underpin EML4-ALK driven cancers and their response to targeted drugs". Cellular and Molecular Life Sciences. 73 (6): 1209–1224. doi:10.1007/s00018-015-2117-6. PMC 4761370. PMID 26755435.
- 1 2 Ellis PM, Blais N, Soulieres D, et al. (June 2011). "A Systematic Review and Canadian Consensus Recommendations on the Use of Biomarkers in the Treatment of Non-small Cell Lung Cancer". J Thorac Oncol. 6 (8): 1379–91. doi:10.1097/JTO.0b013e318220cb8e. PMID 21709590.
- ↑ Japan becomes first country to approve Roche’s alectinib for people with a specific form of advanced lung cancer
- ↑ New Oral Therapy To Treat ALK-Positive Lung Cancer. Dec 2015