EML4-ALK positive lung cancer is a primary
malignant
Malignancy () is the tendency of a medical condition to become progressively worse.
Malignancy is most familiar as a characterization of cancer. A ''malignant'' tumor contrasts with a non-cancerous ''benign'' tumor in that a malignancy is not s ...
lung tumor
Lung tumors are neoplastic lung nodules. These include:
Primary tumors of the lung/pulmonary system:
* Bronchial leiomyoma, a rare, benign tumor
* Lung cancer, the term commonly used to refer to ''carcinoma of the lung''
* Pulmonary carcinoid ...
whose
cells contain a characteristic abnormal configuration of
DNA wherein the ''echinoderm microtubule-associated protein-like 4'' (''
EML4'')
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
is fused to the ''
anaplastic lymphoma kinase
Anaplastic lymphoma kinase (ALK) also known as ALK tyrosine kinase receptor or CD246 (cluster of differentiation 246) is an enzyme that in humans is encoded by the ''ALK'' gene.
Identification
Anaplastic lymphoma kinase (ALK) was originally dis ...
'' (''ALK'')
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
. This abnormal
gene fusion A fusion gene is a hybrid gene formed from two previously independent genes. It can occur as a result of translocation, interstitial deletion, or chromosomal inversion. Fusion genes have been found to be prevalent in all main types of human neopla ...
leads to the production of a
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...
(
EML4-ALK) that appears, in many cases, to promote and maintain the malignant behavior of the
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...
cells.
The transforming ''EML4-ALK'' fusion gene was first reported in non-small cell lung carcinoma (NSCLC) in 2007.
Signs and symptoms
The signs and symptoms of this lung cancer variant seem to mimic those of the underlying major cell type.
Diagnosis
Classification
Most lung carcinomas containing the ''EML4-ALK'' gene fusion are
adenocarcinomas.
Some studies suggest that the
papillary adenocarcinoma
Papillary adenocarcinoma is a histological form of lung cancer that is diagnosed when the malignant cells of the tumor form complex papillary
Papilla (Latin, 'nipple') or papillae may refer to:
In animals
* Papilla (fish anatomy), in the mouth ...
and the
signet ring cell adenocarcinoma
Signet may refer to:
*Signet, Kenya, A subsidiary of the Kenyan Broadcasting Corporation (KBC), specifically set up to broadcast and distribute the DTT signals
* Signet ring, a ring with a seal set into it, typically by leaving an impression in sea ...
variants are more likely to carry this fused gene than other histological variants.
Screening
Screening for ALK positive lung cancer is now a standard of care in the United States and Canada. Screening can be done with immunostaining,
FISH
Fish are aquatic, craniate, gill-bearing animals that lack limbs with digits. Included in this definition are the living hagfish, lampreys, and cartilaginous and bony fish as well as various extinct related groups. Approximately 95% ...
, or next-generation sequencing (NGS).
Treatment
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
Ceritinib (INN, trade name Zykadia , from Novartis) is a prescription-only drug used for the treatment of non-small cell lung cancer (NSCLC). It was developed by Novartis and received FDA approval for use in April 2014..Ceritinib is also sold un ...
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).
Alectinib another second generation targeted therapy and was approved (for this) by Japan in 2014
[Japan becomes first country to approve Roche’s alectinib for people with a specific form of advanced lung cancer]
/ref> and by US FDA
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food s ...
in 2015.,[New Oral Therapy To Treat ALK-Positive Lung Cancer. Dec 2015]
/ref> manufactured by Genentech and marketed under the brand name Alecensa.
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 (FDA approved in 2018), manufactured by Pfizer.
Prognosis
Treatment with crizotinib achieves 60% response rate.
Epidemiology
''EML4-ALK'' gene fusions occur almost exclusively in carcinomas arising in non-smokers.
References
{{Reflist, 2
External links
*Entrez Gen
EML4 echinoderm microtubule associated protein like 4 ''Homo sapiens''
Lung cancer