The EML4-ALK oncogene: targeting an essential growth driver in human cancer

摘要: Targeting of essential growth drivers represents an ideal approach to cancer treatment. To identify such molecules in clinical specimens, we developed a highly sensitive functional screening system based on the preparation retroviral cDNA expression libraries. By library lung adenocarcinoma with focus formation assay, discovered EML4-ALK fusion-type oncogene. A small chromosomal inversion thus leads fusion amino-terminal portion microtubule-associated protein EML4 intracellular kinase domain ALK, receptor-type tyrosine kinase. Constitutive dimerization mediated by motif results activation. Specific inhibitors activity ALK have been as therapeutic drugs for EML4-ALK–positive cancer, three which (crizotinib, ceritinib, and alectinib) already approved use. An overall response rate 93.5% alectinib has shown that agents target can become magic bullets