Biology and targeted therapy of gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the strointestinal tract. Activating mutations of KIT or PDGF receptor alpha (PDGFRA) have been identified in the vast majority of GISTs. Most GISTs are sporadic and some kindred of familiar GIST with a germline mutation in KIT or PDGFRA have been reported. The inhibition of KIT or PDGFRA activity by the kinase inhibitor imatinib frequently results in dramatic clinical responses in advanced cases of GIST. The clinical response to imatinib therapy is correlated with the type of mutation in KIT and PDGFRA. Resistance to imatinib after an initial response has been reported and secondary point mutations in KIT or PDGFRA that confer imatinib resistance are the most common mechanisms responsible for an acquired resistance to imatinib. The determination of KIT and PDGFRA mutations would be useful in predicting the effect of imatinib. GISTs are the first solid tumors to respond well to targeted small molecular therapy. This review outlines the biology and targeted therapy of GISTs.departmental bulletin pape