Gastrointestinal stromal tumors--a review.

Gastrointestinal stromal tumors (GISTs) may be defined as intraabdominal nonepithelial (mesenchymal) tumors that express the KIT protein or have an activating mutation in a class III receptor tyrosine kinase gene (KIT or PDGFRA). GISTs are diagnosed at a frequency of about 15 new cases annually per million, though small indolent GISTs are likely to occur more frequently in the general population. The clinical behavior is variable, and assessment of the malignancy potential is usually based mainly on the size and the proliferation characteristics of the tumor. The overwhelming majority of GISTs express the KIT protein, the transmembrane receptor tyrosine kinase for the stem cell factor. The majority of GISTs harbor a mutation in the KIT proto-oncogene that translates into constitutively activated KIT protein kinase, and a minority have mutated PDGFRA gene resulting in activated platelet-derived growth factor alpha receptor tyrosine kinase. Most GISTs respond to imatinib mesylate, which selectively inhibits both KIT and PDGFRA, and is now considered as the standard systemic therapy for advanced GIST. In contrast, responses to conventional chemotherapy are infrequent (generally less than 10%), but combination therapies with imatinib have not been explored. Research on adjuvant imatinib and novel targeted therapies is ongoing.