EML4-ALK fusion protein

Comprised of portions of the echinoderm microtubule-associated protein-like 4 gene (EML4) on chromosome 2p21 and the anaplastic lymphoma tyrosine kinase gene (ALK) on 2p23.

EML4ALK fusion protein gene is mutually exclusive of EGFR mutations.

About 5% of lung adenocarcinomas harbor the onchogenic fusion of EMLA4-ALK which is more prevalent in never or light smokers with tumors generally in younger patients with tumors that are wild type for EGFR and KRAS.

Anaplastic lymphoma kinase rearrangement occurs in approximately 3-7% of patients with non-small cell lung cancer and targeted therapy with ALK tyrosine kinase inhibitors are effective in this patient subset.

In a small proportion of lung cancer patients ALK rearrangements are present and is a result of a small inversion within chromosome 2p, leading to a fusion of a portion of the EML4 gene with exons 20 through 29 of ALK.

A potent gene that activates signal transduction cascade, promotes tumor cell proliferation and survival.

Found in one fourth of nonsmokers with lung cancer and in 3-5% of all patients with non-small cell lung cancer.

Crizotinib, and oral active ALK inhibitor has received 57% overall response rate, 87% disease control rate and 6 month progression free survival of 72% in heavily pretreated patients with adenocarcinoma (Bang Y et al).

Additional drugs approved certinib (Zykadia), alectinib (Alcensa and Brigatinib (Alumbrig) for ALK postivie NSCLC.

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