There is now considerable interest in gastrointestinal stromal tumor (GIST) 
because it can be treated effectively with a targeted molecular agent. The 
majority of GISTs contain an activating mutation in the KIT protooncogene or, 
occasionally, in the platelet-derived growth factor-alpha (PDGFRA) gene. Five 
years ago, imatinib mesylate, a specific molecular inhibitor of the protein 
products of these 2 genes, was applied to metastatic GIST. Approximately 80% of 
patients with metastatic GIST benefit from imatinib, although acquired 
resistance to the agent may develop. For patients with primary GIST, surgery 
remains the treatment of choice, and whether outcome is improved by adjuvant 
imatinib is currently under broad investigation. A combination of imatinib 
therapy and surgery also may be effective in a subset of patients with 
metastatic or unresectable primary GIST. In this review, the authors summarize 
the new multimodality approach to GIST. The integration of surgery and molecular 
therapy in GIST will serve as a prototype for the management of other solid 
tumors for which targeted agents become available.