Gastrointestinal stromal tumours (GIST)

Gastrointestinal stromal tumours (GIST) are rare malignant mesenchymal tumours caused by a functional mutation in c-kit or PDGF-A. Imatinib mesylate, a small molecule that targets KIT, PDGFR and ABL6BCR, has significantly changed the management and prognosis of these tumours. Although surgery remains the first-line treatment for localised GIST, patients respond to imatinib mesylate in 85 % of cases treated for metastatic disease, with a median time to progression of 2 years and a median survival of 5 years, compared with 12 months before imatinib treatment. The natural history of GIST and the outcome of imatinib mesylate treatment are strongly correlated with the tumour molecular characteristics, particularly its mutational status. A better understanding of the molecular processes will make it possible to optimise patient care, particularly with regard to determining the place of surgery in treating advanced disease, the role of imatinib exposure in the kinetics of emergent resistance, imatinib as an adjuvant treatment in high-risk, non-metastatic disease, and the future of newly available targeted molecules, such as sunitinib.