title: Systemic therapy for advanced gastrointestinal stromal tumors: beyond imatinib.
abstract: 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.
authors: Department of Internal Medicine, Division of Hematology and Oncology, University of Michigan, Ann Arbor, Michigan 48109-5934, USA.
authors: Edward J
authors: EJ
authors: Kim
authors: Mark M
authors: MM
authors: Zalupski
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D000068877:Imatinib Mesylate; D007211:Indoles / Q000627:therapeutic use; D009154:Mutation; D010879:Piperazines / Q000627:therapeutic use*; D010880:Piperidines; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011725:Pyridines; D011743:Pyrimidines / Q000627:therapeutic use*; D011758:Pyrroles / Q000627:therapeutic use; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics; D000077210:Sunitinib; D013844:Thiazoles / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D007211:Indoles; D010879:Piperazines; D010880:Piperidines; D011725:Pyridines; D011743:Pyrimidines; D011758:Pyrroles; D013844:Thiazoles; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; D017479:Receptors, Platelet-Derived Growth Factor; C498826:nilotinib; C526575:masitinib; D000077210:Sunitinib