The insulin-like growth factor system as a potential therapeutic target in gastrointestinal stromal tumors.

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.

• Authors: Martin G Belinsky, Lori Rink, Kathy Q Cai, Michael F Ochs, Burton Eisenberg, Min Huang, Margaret von Mehren, Andrew K Godwin
• Journal: Cell cycle (Georgetown, Tex.) (Cell Cycle) Vol. 7 Issue 19 Pg. 2949-55 (Oct 2008) ISSN: 1551-4005 [Electronic] United States
• PMID: 18818517 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Benzamides
• Piperazines
• Pyrimidines
• Somatomedins
• Imatinib Mesylate
• Proto-Oncogene Proteins c-ret

Topics

• Benzamides
• Gastrointestinal Stromal Tumors (drug therapy, pathology)
• Humans
• Imatinib Mesylate
• Piperazines (metabolism, pharmacology)
• Proto-Oncogene Proteins c-ret (antagonists & inhibitors, genetics, metabolism)
• Pyrimidines (metabolism, pharmacology)
• Signal Transduction
• Somatomedins (antagonists & inhibitors, metabolism, therapeutic use)