Gastrointestinal stromal tumors (GIST) represent 20-40% of human sarcomas.Whereas approximately one-half of GIST can be cured by surgery, prognosis of advanced disease used to be poor due to the high inherent resistance of these tumors to conventional chemo-and radiotherapy.The introduction of molecularly targeted therapy e.g.with imatinibmesylate following the discovery of the role of oncogenic mutations in the receptor tyrosine kinases KIT and PDGFRA has significantly increased patient survival.However,these treatments fail to eradicate GIST cells in 95-97% of patients who eventually progress and die from the disease due to the emergence of clones with drug-resistant mutations.