title: Imatinib-refractory gastrointestinal stromal tumors: the clinical problem and therapeutic strategies.
abstract: Treatment of gastrointestinal stromal tumor (GIST) is a paradigm for targeted therapy. These mesenchymal tumors are refractory to standard chemotherapy and radiation therapy. Targeted therapy has successfully exploited the oncologic drivers of GIST--the tyrosine kinases, KIT, and the platelet-derived growth factor receptor. Therapy with imatinib has dramatically altered the natural history of patients with advanced GIST. However, patients are developing resistance to imatinib and thus presenting with a major clinical challenge. Alternative approaches to imatinib-refractory disease are needed. Newer approaches using biologic data regarding the mechanisms of resistance are being tested alone or in combination with imatinib and are the focus of this review. Effective novel agents for imatinib-refractory GIST used as single agents or in combination with imatinib will likely become future regimens to be tested in first-line metastatic disease and in the adjuvant setting.
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. margaret.vonmehren@fccc.edu
authors.forename: Margaret
authors.initials: M
authors.lastname: von Mehren
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D000068877:Imatinib Mesylate; D008495:Medical Oncology / Q000639:trends; D010879:Piperazines / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D040262:Receptors, Vascular Endothelial Growth Factor