Insulin-like growth factor 1 receptor (IGF-1R): A potential therapeutic target for gastrointestinal stromal tumors (GIST)

10507 Background: Most GISTs possess a gain-of-function mutation in c-KIT or PDGFRα, which are targets of imatinib mesylate. However, wild type (WT) GIST and pediatric GIST lack mutations in either gene. These GISTs tend to be less responsive to imatinib-based therapies and have a poor prognosis. Overexpression of IGF-1R has been identified in many tumor types and inhibitors are currently being studied clinically. We identified amplification of IGF1R in a SNP analysis of GIST tumors and thus studied its potential as a therapeutic target in WT and mutant GIST. Methods: Expression of IGF-1R and downstream effectors in clinical GIST samples were examined using immunoblots and immunohistochemistry. Copy number changes of the IGF1R gene were examined by genomic qPCR and FISH. The role of IGF-1R in GIST signaling and viability were analyzed using NVP-AEW541 (Novartis, Basel, Switzerland), a specific inhibitor of IGF-1R, alone and in combination with imatinib, or via siRNA silencing of IGF1R. Results: IGF-1R was...

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