• 1
    Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002; 347: 472-480.
  • 2
    Verweij J, Casali PG, Zalcberg J, et al. Progression-free survival in gastrointestinal stromal tumors with high-dose imatinib: randomized trial. Lancet. 2004; 364: 1127-1134.
  • 3
    Van Glabbeke M, Verweij J, Casali PG, et al. Initial and late resistance to imatinib in advanced gastrointestinal stromal tumors are predicted by different prognostic factors: a European Organisation for Research and Treatment of Cancer-Italian Sarcoma Group-Australasian Gastrointestinal Trials Group study. J Clin Oncol. 2005; 23: 5795-5804.
  • 4
    Debiec-Rychter M, Sciot R, Le Cesne A, et al. EORTC Soft Tissue and Bone Sarcoma Group; The Italian Sarcoma Group; Australasian GastroIntestinal Trials Group. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumors. Eur J Cancer. 2006; 42: 1093-1103.
  • 5
    Bauer S, Hubert C, Heinrich MC, Cohen P, Bertagnolli M, Demetri GD. KIT hyperactivation in imatinib-resistant GIST: implication for salvage therapies. ASCO. 2005; 824s.
  • 6
    Antonescu CR, Besmer P, Guo T, et al. Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res. 2005; 11: 4182-4190.
  • 7
    Debiec-Rychter M, Cools J, Dumez H, et al. Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants. Gastroenterology. 2005; 128: 270-279.
  • 8
    Wardelmann E, Merkelbach-Bruse S, Pauls K, et al. Polyclonal evolution of multiple secondary KIT mutations in gastrointestinal stromal tumors under treatment with imatinib mesylate. Clin Cancer Res. 2006; 12: 1743-1749.
  • 9
    Heinrich MC, Corless CL, Blanke CD, et al. Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J Clin Oncol. 2006; 24: 4764-4774.
  • 10
    Bauer S, Duensing A, Demetri GD, Fletcher JA. KIT oncogenic signaling mechanisms in imatinib-resistant gastrointestinal stromal tumor: PI3-kinase/AKT is a crucial survival pathway. Oncogene. 2007; 26: 7560-7568.
  • 11
    Mahadevan D, Riley C, Simons B, et al. Mechanisms of Gleevec resistance in GIST and potential therapeutic interventions. AACR. 2005; 507s.
  • 12
    Scotlandi K, Manara MC, Stramiello R, et al. C-kit receptor expression in Ewing sarcoma: lack of prognostic value but therapeutic targeting opportunities in appropriate conditions. J Clin Oncol. 2003; 21: 1952-1960.
  • 13
    Gonzalez I, Andreu EJ, Panizo A, et al. Imatinib inhibits proliferation of Ewing tumor cells mediated by the stem cell factor/KIT receptor pathway, and sensitizes cells to vincristine and doxorubicin-induced apoptosis. Clin Cancer Res. 2004; 10: 751-761.
  • 14
    Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst. 2000; 92: 205-210.
  • 15
    Young H, Baum R, Cremerius U, et al. Measurement of clinical and subclinical tumor response using (18F)-fluorodeoxyglucose and positron emission tomography: review and 1999 EORTC recommendations. European Organization for Research and Treatment of Cancer (EORTC) PET Study Group. Eur J Cancer. 1999; 35: 1773-1782.
  • 16
    Loewe S. The problem of synergism and antagonism of combined drugs. Arzneimittelforschung. 1953; 3: 285-290.
  • 17
    Berenbaum MC. Criteria for analyzing interactions between biologically active agents. Adv Cancer Res. 1981; 35: 269-335.
  • 18
    Steel GG, Peckman MJ. Exploitable mechanisms in combined radiotherapy-chemotherapy: the concept of additivity. Int J Radiat Oncol Biol Phys. 1979; 5: 85-93.
  • 19
    Tallarida RJ. Drug synergism: its detection and applications. J Pharmacol Exp Ther. 2001; 298: 865-872.
  • 20
    Martins AS, Ordonez JL, Garcia-Sanchez A, et al. A pivotal role for heat shock protein 90 in Ewing sarcoma resistance to anti-insulin-like growth factor 1 receptor treatment: in vitro and in vivo study. Cancer Res. 2008; 68: 6260-6270.
  • 21
    Martins AS, Mackintosh C, Herrero-Martín D, et al. IGF1R pathway inhibition by ADW742, alone or in combination with imatinib, doxorubicin or vincristine, is a novel therapeutic approach in Ewing tumor. Clin Cancer Res. 2006; 12( 11 pt 1): 3532-3540.
  • 22
    Van Glabbeke M, van Oosterom AT, Oosterhuis JW, et al. Prognostic factors for the outcome of chemotherapy in advanced soft tissue sarcoma: an analysis of 2185 patients treated with anthracycline-containing first-line regimens. A European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study. J Clin Oncol. 1999; 17: 150-157.
  • 23
    Drevs J, Fakler J, Eisele S, et al. Antiangiogenic potency of various chemotherapeutic drugs for metronomic chemotherapy. Anticancer Res. 2004; 24: 1759-1763.
  • 24
    Browder T, Butterfield CE, Kraling BM, et al. Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res. 2000; 60: 1878-1886.
  • 25
    Pietras K, Hanahan D. A multitargeted, metronomic, and maximum-tolerated dose “chemo-switch” regimen is antiangiogenic, producing objective responses and survival benefit in a mouse model of cancer. J Clin Oncol. 2005; 23: 939-952.
  • 26
    Janeway KA, Liegl B, Harlow A, et al. Pediatric KIT wild-type and platelet-derived growth factor receptor alpha-wild-type gastrointestinal stromal tumors share KIT activation but not mechanisms of genetic progression with adult gastrointestinal stromal tumors. Cancer Res. 2007; 67: 9084-9088.
  • 27
    Tarn C, Rink L, Merkel E, et al. Insulin-like growth factor 1 receptor is a potential therapeutic target for gastrointestinal stromal tumors. Proc Natl Acad Sci U S A. 2008; 105: 8387-8392.
  • 28
    Liegl B, Kepten I, Le C, et al. Heterogeneity of kinase inhibitor resistance mechanisms in GIST. J Pathol. 2008; 216: 64-74.
  • 29
    Heinrich MC, Owzar K, Corless CL, et al. Correlation of kinase genotype and clinical outcome in the North American Intergroup Phase III Trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group. J Clin Oncol. 2008; 26: 5360-5367.
  • 30
    Heinrich MC, Maki RG, Corless CL, et al. Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J Clin Oncol. 2008; 26: 5352-5359.
  • 31
    Bauer S, Yu LK, Demetri GD, Fletcher JA. Heat shock protein 90 inhibition in imatinib-resistant gastrointestinal stromal tumor. Cancer Res. 2006; 66: 9153-9161.
  • 32
    Wiebe L, Kasza KE, Maki RG, et al. Activity of sorafenib (SOR) in patients (pts) with imatinib (IM) and sunitinib (SU)-resistant (RES) gastrointestinal stromal tumors (GIST): a phase II trial of the University of Chicago Phase II Consortium. Proc ASCO. 2008; 553s.
  • 33
    Wagner AJ, Morgan JA, Chugh R, et al. Inhibition of heat shock protein (Hsp90) with the novel agent IPI-504 in metastatic GIST following failure of tyrosine kinase inhibitors (TKIs) or other sarcomas: clinical results from phase 1 trial. Proc ASCO. 2008; 553s.
  • 34
    Mahadevan D, Cooke L, Riley C, et al. A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors. Oncogene. 2007; 26: 3909-3919.
  • 35
    Prior JO, Montemurro M, Orcurto MV, et al. Early prediction of response to sunitinib after imatinib failure by 18F-fluorodeoxyglucose positron emission tomography in patients with gastrointestinal stromal tumor. J Clin Oncol. 2009; 27: 439-445.
  • 36
    Kerkela R, Grazette L, Yacobi R, et al. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med. 2006; 12: 908-916.
  • 37
    Ribeiro AL, Marcolino MS, Bittencourt HNS, et al. An evaluation of the cardiotoxicity of imatinib mesylate. Leuk Res. 2008; 32: 1809-1814.
  • 38
    Perik PJ, Rikhof B, de Jong FA, et al. Results of plasma N-terminal pro B-type natriuretic peptide and cardiac troponin monitoring in GIST patients do not support the existence of imatinib-induced cardiotoxicity. Ann Oncol. 2008; 19: 359-361.