Targeted therapies in gastrointestinal stromal tumours (GIST): Results and promises

Gastrointestinal stromal tumours (GIST) are rare soft tissue sarcomas arising primarily from mesenchymal tissue in the gastrointestinal tract and abdomen. GISTs are diagnosed by strong and diffuse positive immunohistochemical staining of the proto-oncogene c-kit, a type III tyrosine kinase receptor. Approximately 80% of cases have mutated KIT codifying gene, and 5% have mutated platelet-derived growth factor receptor A (PDGFRA). The identification of these mutations as a key factor in the pathogenesis of GIST has substantially altered the diagnosis and treatment of GIST. Imatinib, a molecularly targeted drug that inhibits the kinase activity of KIT and PDGFRs, has been shown to be highly efficacious in patients with advanced GIST. However, early or late tumour resistance to imatinib is an increasing clinical problem. Sunitinib, a multitargeted tyrosine-kinase inhibitor with antiangiogenic activity, is an effective therapeutic option for patients with advanced disease after failure of imatinib treatment.