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.
Contents
The transforming EML4-ALK fusion gene was first reported in non-small cell lung carcinoma (NSCLC) in 2007.
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 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. About 4% of non-small-cell lung carcinomas involve an EML4-ALK tyrosine kinase fusion gene. 4–6% of lung adenocarcinomas involve the fusion gene.
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.
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.
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 and by US FDA in 2015.
Prognosis
Treatment with crizotinib achieves 60% response rate.