Companion Diagnostic for ALK Mutations

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Kinase inhibitors such as Gleevec and Tarceva have markedly improved cancer therapy. Essential to the use of such inhibitors are companion diagnostics enabling determination of the mutational status of th eir kinase targets in tumors. Anaplastic lymphoma kinase (ALK) fusion oncogenes have emerged as an important cause of lung cancer, and ALK inhibitor programs (by Pfizer, Lil ly, Ariad, Astell as, Zenobia, and others) are in progress, ALK inhibition causes marked anti-tumor responses, but only in patients whose tumors conta in mutant ALK. Both immunohistochemistry (IHe) and fluorescence in situ hybridization (FISH) can identify ALK mutations, but each has multiple limitations Herein, we propose development of a microarray¿based test to ident ify ALK fus ions (EML4¿ALK. NPM¿ALK, CL TC-ALK, and others) from FFPE tissues as a rapid, highly specific and sensit ive companion diagnostic. Insight Genetics has established collaborations with experts in the genetics of ALK and lung cancer, as well as collaborations with pharmaceutical companies developing ALK inhibitors. In the studies proposed, we wi ll establish and validate our ALK mutation detection platform using lung cancer specimens. many also characte rized by ALK FISH and/or IHC to benchmark our assay against these methodolog ies. The Insight Genetics ALK microarray will enable personalized therapy by caregive rs, tra ns lating to improved patient outcomes.