EML4-ALK positive lung cancer

src: clincancerres.aacrjournals.org

EML4-ALK positive lung cancer is a medical term that refers to a primary malignant lung tumor whose cells contain characteristic abnormal DNA configurations in which proteins such as microtubules are associated-such as echinodermia 4 EML4 ) genes are integrated into the anaplastic lymphoma kinase genes ( ALK ). The fusion of these abnormal genes leads to the production of proteins (EML4-ALK) that appear, in many cases, to promote and maintain the malignant behavior of cancer cells.

The transformation fusion gene EML4-ALK was first reported in non-small cell lung carcinoma (NSCLC) in 2007.

Video EML4-ALK positive lung cancer

Classification

Most lung carcinomas that contain the fusion of the EML4-ALK gene are adenocarcinomas.

Several studies have shown that papillary adenocarcinoma and the cell variant of cell adenocarcinoma of the minerals are more likely to carry this fused gene than other histologic variants.

Maps EML4-ALK positive lung cancer

Epidemiology

EML4-ALK gene fusion occurs almost exclusively in carcinomas that occur in non-smokers. About 4% of small non-cell lung carcinomas involve the fusion gene of the EML4-ALK tyrosine kinase. 4-6% of pulmonary adenocarcinomas involve fusion genes.

EML4-ALK mutations are rare in combination with K-RAS or EGFR mutations.

src: clincancerres.aacrjournals.org

Signs and symptoms

The signs and symptoms of this variant of lung cancer seem to mimic those of the underlying primary cell type.

src: www.pnas.org

Screening

A 2011 consensus recommendation from 37 Canadian lung cancer specialists found that, in June 2011, there was insufficient evidence to recommend routine screening of lung cancer specimens for EML4-ALK fusion, but that could soon change.

There is a companion diagnostic test to detect the EML4-ALK fusion protein.

src: mcr.aacrjournals.org

Treatment

Crizotinib is a targeted therapy (FDA-approved in 2011), manufactured by Pfizer and marketed under the brand names Xalkori and Crizalk that target the EML4/ALK fusion gene.

Ceritinib is a second-generation target therapy (FDA-approved in 2014), manufactured by Novartis and sold under the brand name Zykadia which also targets the EML4 fusion gene, but as second-generation drugs have smaller molecules that allow superior penetration of the Blood. Brain Barrier (BBB) ​​above Crizotinib and better able to protect Central Nervous System (CNS).

Second generation Alectinib targeted therapy and approved (for this) by Japan in 2014 and by the US FDA by 2015., manufactured by Genentec and marketed under the brand name Alecensa.

Brigatinib second-generation target therapy (FDA approved in 2017), manufactured by Takeda and marketed under the Alunbrig trademark.

Ensartinib is a second-generation target therapy (experimental drug X-396), produced by XCovery.

Lorlatinib is a third-generation target therapy (awaiting FDA approval under experimental drug PF-6463922), manufactured by Pfizer.

TPX-0005 is a new third-generation targeted therapeutic drug trial.

src: clincancerres.aacrjournals.org

Prognosis

Treatment with crizotinib achieved a 60% response rate. However, crizotinib showed no improvement in overall survival compared with chemotherapy. This may be due to the fact that there is a 70% crossover rate to crizotinib in patients treated initially with chemotherapy. Also, patients who tested negative for EML4/ALK fusion had a crizotinib response rate of up to 35%.

src: clincancerres.aacrjournals.org

References

src: cancergrace.org

External links

• Entrez Gene EML4 echinoderm microtubule related proteins such as 4 Homo sapiens
• Patients Lung Cancer Patients Positive and Caregiver Support: https://www.alkpositive.org/

Source of the article : Wikipedia