EML4-ALK fusion protein
From Standard of Care
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.
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 nonsmoker is 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).