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 PDGFRα. Therapy for GISTs has been revolutionized by the use of the selective tyrosine kinase inhibitor imatinib mesylate (IM). For the subset (∼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.
Original language | English (US) |
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Pages (from-to) | 2949-2955 |
Number of pages | 7 |
Journal | Cell cycle (Georgetown, Tex.) |
Volume | 7 |
Issue number | 19 |
State | Published - Oct 1 2008 |
Keywords
- GISTs
- Imatinib mesylate
- Insulin growth factor
- NYP-AEW541
- Tyrosine kinase inhibitors
ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
- Developmental Biology