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Belinsky MG , Rink L , Cai KQ , Ochs MF , Eisenberg B , Huang M , von Mehren M , Godwin AK
The insulin-like growth factor system as a potential therapeutic target in gastrointestinal stromal tumors
Cell Cycle. 2008 Oct;7(19) :2949-55
PMID: 18818517    PMCID: PMC2626174   
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Abstract
The majority of gastrointestinal stromal tumors (GISTs) are characterized by oncogenic gain-of-function mutations in the receptor tyrosine kinase (RTK) c-KIT with a minority in PDGFRalpha. Therapy for GISTs has been revolutionized by the use of the selective tyrosine kinase inhibitor imatinib mesylate (IM). For the subset (approximately 10-15%) of GISTs that lack oncogenic mutations in these receptors, the genetic changes driving tumorigenesis are unknown. We recently reported that the gene encoding the insulin-like growth factor 1 receptor (IGF-1R) is amplified in a subset of GISTs, and the IGF-1R protein is overexpressed in wild-type and pediatric GISTs. In this report we present a more complete picture of the involvement of components of the insulin-like growth factor-signaling pathway in the pathogenesis of GISTs. We also discuss how the IGF pathway may provide additional molecular targets for the treatment of GISTs that respond poorly to IM therapy.
Notes
Belinsky, Martin G Rink, Lori Cai, Kathy Q Ochs, Michael F Eisenberg, Burton Huang, Min von Mehren, Margaret Godwin, Andrew K AG106588/AG/NIA NIH HHS/United States CA009035-31/CA/NCI NIH HHS/United States P30 CA006927/CA/NCI NIH HHS/United States U10 CA21661/CA/NCI NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review United States Cell cycle (Georgetown, Tex.) Cell Cycle. 2008 Oct;7(19):2949-55. Epub 2008 Oct 7.