Current clinical management of gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GIST) are defined as c-KIT-positive mesenchymal neoplasias located in the gastrointestinal tract and abdomen, most of which present an activating KIT mutation, a fundamental step in the development of disease. However, recent studies reported a small subgroup of KIT-negative GIST, in which platelet-derived growth factor receptor A, protein kinase C-tau, and FLJ10261 expression was detected. Imatinib (Gleevec, Novartis) is an orally administered competitive inhibitor of the tyrosine kinase domain of receptors such as KIT, ABL, and BCR-ABL fusion proteins, and the platelet-derived growth factor receptor. Phase I-III clinical trials have demonstrated the efficacy of imatinib in the treatment of metastatic GIST. However, the optimal dose and role of imatinib in an adjuvant or neoadjuvant setting have yet to be defined. Therefore, further studies investigating the mechanism of resistance to imatinib in patients with GIST are warranted.