Systemic Therapy for Advanced Gastrointestinal Stromal Tumors: Beyond Imatinib

Progression on first-line therapy with imatinib in gastrointestinal stromal tumors (GIST) is caused by either initial resistance or more often a secondary mutation in tyrosine kinases KIT or PDGFR. Therapies in development for imatinib-resistant GIST include agents that target KIT/PDGFR with greater potency or possess broader kinase inhibition profiles including VEGFR. To circumvent secondary mutations in KIT/PDGFR, inhibition of the downstream signaling in PI3K/Akt/mTOR pathway and enhanced degradation of KIT/PDGFR are also under investigation. J. Surg. Oncol. 2011;104:901-906. (C) 2011 Wiley Periodicals, Inc.