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.
The transforming EML4-ALK fusion gene was first reported in non-small cell lung carcinoma (NSCLC) in 2007.
Most lung carcinomas containing the EML4-ALK gene fusion are adenocarcinomas.
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.
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.
There is a companion diagnostic test to detect the EML4-ALK fusion protein.
Crizotinib is a targeted therapy (FDA approved in 2011), manufactured by Pfizer and marketed under the brand name Xalkori and Crizalk that targets the EML4/ALK fusion gene.
Ceritinib is a second generation targeted therapy (FDA approved in 2014), manufactured by Novartis and sold under the brand name Zykadia that also targets the EML4 fusion gene, but as a second generation drug it has a smaller molecule that allows superior penetration of the Blood Brain Barrier (BBB) over Crizotinib and is more capable of protecting the Central Nervous System (CNS).
Brigatinib a second generation targeted therapy (FDA approved in 2017), manufactured by Takeda and is marketed under the brand name Alunbrig.
Ensartinib is a second generation targeted therapy (trial drug X-396), manufactured by XCovery.
Lorlatinib is a third generation targeted therapy (awaiting FDA approval under trial drug PF-6463922), manufactured by Pfizer.
TPX-0005 is a new third generation targeted therapy drug trial.
Treatment with crizotinib achieves 60% response rate. However, crizotinib showed no improvement on overall survival compared to chemotherapy. This may be due to the fact that there was a 70% crossover rate to crizotinib in patients treated initially with chemotherapy. Also, patients who tested negative for EML4/ALK fusion had a response rate to crizotinib of up to 35%.
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- 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
- Entrez Gene EML4 echinoderm microtubule associated protein like 4 Homo sapiens
- ALK Positive Lung Cancer Patient and Caregiver Support: https://www.alkpositive.org/