Mechanisms of resistance to imatinib and sunitinib in gastrointestinal stromal tumor

Cancer Chemotherapy and Pharmacology

Volumn 67, Issue SUPPL. 1, 2011, Pages

  Wang, Wei Lien ^a   Conley, Anthony ^a   Reynoso, David ^a   Nolden, Laura ^a   Lazar, Alexander J ^a   George, Suzanne ^b   Trent, Jonathan C ^a  

^a UNIVERSITY OF TEXAS   (United States)

^b DANA FARBER CANCER INSTITUTE   (United States)

Author keywords

Gene mutations; GIST; Imatinib resistant disease; Mutated KIT

Indexed keywords

B RAF KINASE INHIBITOR; DASATINIB; HEAT SHOCK PROTEIN 90 INHIBITOR; HISTONE DEACETYLASE INHIBITOR; IMATINIB; NILOTINIB; PLACEBO; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PROTEIN TYROSINE KINASE INHIBITOR; SORAFENIB; STEM CELL FACTOR; SUNITINIB;

ARTICLE; BINDING AFFINITY; CANCER RESISTANCE; DISEASE COURSE; DRUG ABSORPTION; DRUG BLOOD LEVEL; DRUG DOSE COMPARISON; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG MECHANISM; DRUG MEGADOSE; DRUG RECEPTOR BINDING; EXON; GASTROINTESTINAL STROMAL TUMOR; GENE EXPRESSION REGULATION; GENE MUTATION; HUMAN; LOW DRUG DOSE; PATIENT COMPLIANCE; PRIORITY JOURNAL; STEADY STATE;

ANTINEOPLASTIC AGENTS; DISEASE PROGRESSION; DRUG RESISTANCE, NEOPLASM; GASTROINTESTINAL STROMAL TUMORS; HUMANS; INDOLES; MUTATION; PIPERAZINES; PROTEIN KINASE INHIBITORS; PROTO-ONCOGENE PROTEINS C-KIT; PYRIMIDINES; PYRROLES; RECEPTOR, PLATELET-DERIVED GROWTH FACTOR ALPHA;

EID: 79151479118     PISSN: 03445704     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00280-010-1513-8     Document Type: Article

References (82)

1. S Hirota K Isozaki Y Moriyama K Hashimoto T Nishida S Ishiguro K Kawano M Hanada A Kurata M Takeda G Muhammad Tunio, et al. 1998 Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors Science 279 5350 577 580 1:CAS:528:DyaK1cXotVyhsw%3D%3D 10.1126/science.279.5350.577 9438854
2. MC Heinrich C Corless GD Demetri CD Blanke M von Mehren H Joensuu LS McGreevey CJ Chen AD Van de Abbeele BJ Druker B Kiese, et al. 2003 Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor JCO 21 23 4342 4349 1:CAS:528:DC%2BD2cXpsVWqu7Y%3D 10.1200/JCO.2003.04.190
3. LG Kindblom HE Remotti F Aldenborg JM Meis-Kindblom 1998 Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal Am J Pathol 152 5 1259 1269 1:STN:280:DyaK1c3kvVejug%3D%3D 9588894
4. M Miettinen J Lasota 2006 Gastrointestinal stromal tumors: pathology and prognosis at different sites Semin Diagn Pathol 23 2 70 83 10.1053/j.semdp.2006. 09.001 17193820
5. N Price J Trent A El-Naggar D Cogdell E Taylor K Hunt R Pollock L Hood I Shmulevich W Zhang 2007 Highly accurate two-gene classifier for differentiating gastrointestinal stromal tumors and leiomyosarcomas Proc Nat Acad Sci 104 9 3414 3419 1:CAS:528:DC%2BD2sXjtVCntrk%3D 10.1073/pnas.0611373104 17360660
6. JC Trent J Beach MA Burgess N Papadopolous LL Chen RS Benjamin SR Patel 2003 A two-arm phase II study of temozolomide in patients with advanced gastrointestinal stromal tumors and other soft tissue sarcomas Cancer 98 12 2693 2699 1:CAS:528:DC%2BD2cXit1ygsw%3D%3D 10.1002/cncr.11875 14669291
7. CD Mol DR Dougan TR Schneider RJ Skene ML Kraus DN Scheibe GP Snell H Zou BC Sang KP Wilson 2004 Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase J Biol Chem 279 30 31655 31663 1:CAS:528:DC%2BD2cXlslOrtrc%3D 10.1074/jbc.M403319200 15123710
8. Woodman S, Trent JC (2009) Unpublished data
9. JC McAuliffe KK Hunt AJ Lazar H Choi W Qiao P Thall RE Pollock RS Benjamin JC Trent 2009 A randomized, phase II study of preoperative plus postoperative imatinib in GIST: evidence of rapid radiographic response and temporal induction of tumor cell apoptosis Ann Surgical Oncol 16 4 910 919 10.1245/s10434-008-0177-7
10. McAuliffe J, Lazar A, Yang D, Araujo D, Qiao W, Thall P, Raymond A, Benjamin R, Trent J (2007) Association of intra-tumoral vascular endothelial growth factor expression and clinical outcome for patients with gastrointestinal stromal tumors treated with imatinib mesylate. Clinical Cancer Research 13(Epub Ahead of Print)
11. Trent JC, Ramdas L, Dupart J, Hunt K, Taylor E, Hu L, Salvado A, Abbruzzese JL, Benjamin RS, Pollock R, Zhang W (2006) Early effects of imatinib mesylate on expression of insulin-like growth factor binding protein-3 and positron emission tomography in patients with gastrointestinal stromal tumor. Cancer (manuscript in press)
12. DeMatteo R, Owzar K, Maki R, Pisters P, Blackstein M, Antonescu C, Blanke C, Demetri G, Mehren Mv, Ballman K (2007) Adjuvant imatinib mesylate increases recurrence free survival (RFS) in patients with completely resected localized primary gastrointestinal stromal tumor (GIST): North American Intergroup Phase III trial ACOSOG Z9001. Abstract 10079. American Society of Clinical Oncology Annual Meeting, Chicago
13. MC Heinrich K Owzar CL Corless D Hollis EC Borden CD Fletcher CW Ryan M von Mehren CD Blanke C Rankin RS Benjamin, et al. 2008 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 Clinical Oncol 26 33 5360 5367 1:CAS:528:DC%2BD1MXhslCmug%3D%3D 10.1200/JCO.2008.17.4284
14. S Bauer LK Yu GD Demetri JA Fletcher 2006 Heat shock protein 90 inhibition in imatinib-resistant gastrointestinal stromal tumor Cancer Res 66 18 9153 9161 1:CAS:528:DC%2BD28Xps1aiu74%3D 10.1158/0008-5472.CAN-06-0165 16982758
15. S Sleijfer E Wiemer C Seynaeve J Verweij 2007 Improved insight into resistance mechanisms to imatinib in gastrointestinal stromal tumors: a basis for novel approaches and individualization of treatment Oncologist 12 6 719 726 1:CAS:528:DC%2BD2sXosF2gsLo%3D 10.1634/theoncologist.12-6-719 17602061
16. CD Blanke C Rankin GD Demetri CW Ryan M von Mehren RS Benjamin AK Raymond VH Bramwell LH Baker RG Maki M Tanaka, et al. 2008 Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033 J Clinical Oncol 26 4 626 632 1:CAS:528:DC%2BD1cXis1alsLs%3D 10.1200/JCO.2007.13.4452
17. CD Blanke GD Demetri M von Mehren MC Heinrich B Eisenberg JA Fletcher CL Corless CD Fletcher PJ Roberts D Heinz E Wehre, et al. 2008 Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT J Clinical Oncol 26 4 620 625 1:CAS:528: DC%2BD1cXis1alsL0%3D 10.1200/JCO.2007.13.4403
18. AW Gramza CL Corless MC Heinrich 2009 Resistance to tyrosine kinase inhibitors in gastrointestinal stromal tumors Clin Cancer Res 15 24 7510 7518 1:CAS:528:DC%2BD1MXhsFGgurrO 10.1158/1078-0432.CCR-09-0190 20008851
19. MC Heinrich CL Corless GD Demetri CD Blanke M von Mehren H Joensuu LS McGreevey CJ Chen AD Van den Abbeele BJ Druker B Kiese, et al. 2003 Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor J Clin Oncol 21 23 4342 4349 1:CAS:528:DC%2BD2cXpsVWqu7Y%3D 10.1200/JCO.2003.04.190 14645423
20. CL Corless MC Heinrich 2008 Molecular pathobiology of gastrointestinal stromal sarcomas Annu Rev Pathol 3 557 586 1:CAS:528:DC%2BD1cXjsFersbw%3D 10.1146/annurev.pathmechdis.3.121806.151538 18039140
21. CL Corless A Schroeder D Griffith A Town L McGreevey P Harrell S Shiraga T Bainbridge J Morich MC Heinrich 2005 PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib J Clin Oncol 23 23 5357 5364 1:CAS:528:DC%2BD2MXpslOrtLY%3D 10.1200/JCO.2005.14.068 15928335
22. M Miettinen LH Sobin J Lasota 2005 Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up Am J Surg Pathol 29 1 52 68 10.1097/01.pas.0000146010.92933.de 15613856
23. S Hirota A Ohashi T Nishida K Isozaki K Kinoshita Y Shinomura Y Kitamura 2003 Gain-of-function mutations of platelet-derived growth factor receptor alpha gene in gastrointestinal stromal tumors Gastroenterology 125 3 660 667 1:CAS:528:DC%2BD3sXnvVSiur8%3D 10.1016/S0016-5085(03)01046-1 12949711
24. ME Blackstein JY Blay C Corless DK Driman R Riddell D Soulieres CJ Swallow S Verma 2006 Gastrointestinal stromal tumours: consensus statement on diagnosis and treatment Can J Gastroenterol 20 3 157 163 16550259
25. E Weisberg RD Wright J Jiang A Ray D Moreno PW Manley D Fabbro E Hall-Meyers L Catley K Podar AL Kung, et al. 2006 Effects of PKC412, nilotinib, and imatinib against GIST-associated PDGFRA mutants with differential imatinib sensitivity Gastroenterology 131 6 1734 1742 1:CAS:528:DC%2BD2sXhtFyltLo%3D 10.1053/j.gastro.2006.09.017 17087936
26. S Bauer CL Corless MC Heinrich O Dirsch G Antoch J Kanja S Seeber J Schutte 2003 Response to imatinib mesylate of a gastrointestinal stromal tumor with very low expression of KIT Cancer Chemother Pharmacol 51 3 261 265 12655446
27. FC Miselli P Casieri T Negri M Orsenigo MS Lagonigro A Gronchi M Fiore PG Casali R Bertulli A Carbone MA Pierotti, et al. 2007 c-Kit/PDGFRA gene status alterations possibly related to primary imatinib resistance in gastrointestinal stromal tumors Clin Cancer Res 13 8 2369 2377 1:CAS:528:DC%2BD2sXkt1enurY%3D 10.1158/1078-0432.CCR-06-1745 17438095
28. SE Al-Batran JT Hartmann F Heidel J Stoehlmacher E Wardelmann C Dechow M Dux JR Izbicki T Kraus T Fischer E Jager 2007 Focal progression in patients with gastrointestinal stromal tumors after initial response to imatinib mesylate: a three-center-based study of 38 patients Gastric Cancer 10 3 145 152 1:CAS:528:DC%2BD2sXhtlKqs7nM 10.1007/s10120-007-0425-8 17922091
29. M Debiec-Rychter J Cools H Dumez R Sciot M Stul N Mentens H Vranckx B Wasag H Prenen J Roesel A Hagemeijer, et al. 2005 Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants Gastroenterology 128 2 270 279 1:CAS:528:DC%2BD2MXitVemsL8%3D 10.1053/j.gastro.2004.11.020 15685537
30. CR Antonescu P Besmer T Guo K Arkun G Hom B Koryotowski MA Leversha PD Jeffrey D Desantis S Singer MF Brennan, et al. 2005 Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation Clin Cancer Res 11 11 4182 4190 1:CAS:528:DC%2BD2MXks1GksLw%3D 10.1158/1078-0432.CCR-04-2245 15930355
31. LR Chirieac JC Trent DM Steinert H Choi Y Yang J Zhang SR Patel RS Benjamin AK Raymond 2006 Correlation of immunophenotype with progression-free survival in patients with gastrointestinal stromal tumors treated with imatinib mesylate Cancer 107 9 2237 2244 1:CAS:528:DC%2BD28Xht1Olt7vL 10.1002/cncr.22226 16998931
32. NP Agaram GC Wong T Guo RG Maki S Singer RP Dematteo P Besmer CR Antonescu 2008 Novel V600E BRAF mutations in imatinib-naive and imatinib-resistant gastrointestinal stromal tumors Genes Chromosomes Cancer 47 10 853 859 1:CAS:528:DC%2BD1cXhtVCrtLrE 10.1002/gcc.20589 18615679
33. C Braconi R Bracci I Bearzi F Bianchi S Sabato A Mandolesi L Belvederesi S Cascinu N Valeri R Cellerino 2008 Insulin-like growth factor (IGF) 1 and 2 help to predict disease outcome in GIST patients Ann Oncol 19 7 1293 1298 1:STN:280:DC%2BD1cvgvVynsw%3D%3D 10.1093/annonc/mdn040 18372285
34. MA Pantaleo A Astolfi M Di Battista MC Heinrich P Paterini K Scotlandi D Santini F Catena MC Manara M Nannini A Maleddu, et al. 2009 Insulin-like growth factor 1 receptor expression in wild-type GISTs: a potential novel therapeutic target Int J Cancer 125 12 2991 2994 1:CAS:528:DC%2BD1MXhtlSqsLrE 10.1002/ijc.24595 19672856
35. C Tarn L Rink E Merkel D Flieder H Pathak D Koumbi JR Testa B Eisenberg M von Mehren AK Godwin 2008 Insulin-like growth factor 1 receptor is a potential therapeutic target for gastrointestinal stromal tumors Proc Natl Acad Sci USA 105 24 8387 8392 1:CAS:528:DC%2BD1cXnvVKrs70%3D 10.1073/pnas.0803383105 18550829
36. L Rink Y Skorobogatko AV Kossenkov MG Belinsky T Pajak MC Heinrich CD Blanke M von Mehren MF Ochs B Eisenberg AK Godwin 2009 Gene expression signatures and response to imatinib mesylate in gastrointestinal stromal tumor Mol Cancer Ther 8 8 2172 2182 1:CAS:528:DC%2BD1MXpvFCnu78%3D 10.1158/1535-7163.MCT-09-0193 19671739
37. J Verweij PG Casali J Zalcberg A LeCesne P Reichardt JY Blay R Issels A van Oosterom PC Hogendoorn M Van Glabbeke R Bertulli, et al. 2004 Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial Lancet 364 9440 1127 1134 1:CAS:528: DC%2BD2cXnvVOiu7o%3D 10.1016/S0140-6736(04)17098-0 15451219
38. LL Chen JC Trent EF Wu GN Fuller L Ramdas W Zhang AK Raymond VG Prieto CO Oyedeji KK Hunt RE Pollock, et al. 2004 A missense mutation in KIT kinase domain 1 correlates with imatinib resistance in gastrointestinal stromal tumors Cancer Res 64 17 5913 5919 1:CAS:528:DC%2BD2cXntFClsr4%3D 10.1158/0008-5472.CAN- 04-0085 15342366
39. F Haller S Detken HJ Schulten N Happel B Gunawan J Kuhlgatz L Fuzesi 2007 Surgical management after neoadjuvant imatinib therapy in gastrointestinal stromal tumours (GISTs) with respect to imatinib resistance caused by secondary KIT mutations Ann Surg Oncol 14 2 526 532 10.1245/s10434-006-9228-0 17139461
40. MC Heinrich CL Corless CD Blanke GD Demetri H Joensuu PJ Roberts BL Eisenberg M von Mehren CD Fletcher K Sandau K McDougall, et al. 2006 Molecular correlates of imatinib resistance in gastrointestinal stromal tumors J Clinical Oncol 24 29 4764 4774 1:CAS:528:DC%2BD28XhtFynsrrN 10.1200/JCO.2006.06.2265
41. E Wardelmann S Merkelbach-Bruse K Pauls N Thomas HU Schildhaus T Heinicke N Speidel T Pietsch R Buettner D Pink P Reichardt, et al. 2006 Polyclonal evolution of multiple secondary KIT mutations in gastrointestinal stromal tumors under treatment with imatinib mesylate Clin Cancer Res 12 6 1743 1749 1:CAS:528:DC%2BD28Xis1Cjs7Y%3D 10.1158/1078-0432.CCR-05-1211 16551858
42. Desai J, Shankar S, Heinrich MC, Fletcher JA, Fletcher CD, Manola J, Morgan JA, Corless CL, George S, Tuncali K, Silverman SG, et al.(2007) Clonal evolution of resistance to imatinib in patients with metastatic gastrointestinal stromal tumors. Clin Cancer Res 13(18 Pt 1):5398-5405
43. B Liegl I Kepten C Le M Zhu GD Demetri MC Heinrich CD Fletcher CL Corless JA Fletcher 2008 Heterogeneity of kinase inhibitor resistance mechanisms in GIST J Pathol 216 1 64 74 1:CAS:528:DC%2BD1cXhtFSrtbbF 10.1002/path.2382 18623623
44. M Van Glabbeke J Verweij PG Casali A Le Cesne P Hohenberger I Ray-Coquard M Schlemmer AT van Oosterom D Goldstein R Sciot PC Hogendoorn, et al. 2005 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 23 24 5795 5804 10.1200/JCO.2005.11.601 16110036
45. T Nishida T Kanda A Nishitani T Takahashi K Nakajima T Ishikawa S Hirota 2008 Secondary mutations in the kinase domain of the KIT gene are predominant in imatinib-resistant gastrointestinal stromal tumor Cancer Sci 99 4 799 804 1:CAS:528:DC%2BD1cXlsFyls7w%3D 10.1111/j.1349-7006.2008.00727.x 18294292
46. KS Gajiwala JC Wu J Christensen GD Deshmukh W Diehl JP DiNitto JM English MJ Greig YA He SL Jacques EA Lunney, et al. 2009 KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients Proc Natl Acad Sci USA 106 5 1542 1547 1:CAS:528:DC%2BD1MXhvVOms78%3D 10.1073/pnas.0812413106 19164557
47. SR McLean M Gana-Weisz B Hartzoulakis R Frow J Whelan D Selwood C Boshoff 2005 Imatinib binding and cKIT inhibition is abrogated by the cKIT kinase domain I missense mutation Val654Ala Mol Cancer Ther 4 12 2008 2015 1:CAS:528:DC%2BD2MXhtlCnsrjJ 10.1158/1535-7163.MCT-05-0070 16373716
48. E Tamborini S Pricl T Negri MS Lagonigro F Miselli A Greco A Gronchi PG Casali M Ferrone M Fermeglia A Carbone, et al. 2006 Functional analyses and molecular modeling of two c-Kit mutations responsible for imatinib secondary resistance in GIST patients Oncogene 25 45 6140 6146 1:CAS:528: DC%2BD28XhtVGgsr7E 10.1038/sj.onc.1209639 16751810
49. KG Roberts AF Odell EM Byrnes RM Baleato R Griffith AB Lyons LK Ashman 2007 Resistance to c-KIT kinase inhibitors conferred by V654A mutation Mol Cancer Ther 6 3 1159 1166 1:CAS:528:DC%2BD2sXivV2ntLg%3D 10.1158/1535-7163.MCT- 06-0641 17363509
50. T Negri GM Pavan E Virdis A Greco M Fermeglia M Sandri S Pricl MA Pierotti S Pilotti E Tamborini 2009 T670X KIT mutations in gastrointestinal stromal tumors: making sense of missense J Natl Cancer Inst 101 3 194 204 1:CAS:528:DC%2BD1MXhs1Oms70%3D 10.1093/jnci/djn477 19176456
51. H Kikuchi K Yamashita T Kawabata M Yamamoto Y Hiramatsu K Kondo M Baba M Ohta K Kamiya T Tanaka S Suzuki, et al. 2006 Immunohistochemical and genetic features of gastric and metastatic liver gastrointestinal stromal tumors: sequential analyses Cancer Sci 97 2 127 132 1:CAS:528:DC%2BD28XitFyqsLo%3D 10.1111/j.1349-7006.2006.00154.x 16441423
52. B Liegl JL Hornick CR Antonescu CL Corless CD Fletcher 2009 Rhabdomyosarcomatous differentiation in gastrointestinal stromal tumors after tyrosine kinase inhibitor therapy: a novel form of tumor progression Am J Surg Pathol 33 2 218 226 10.1097/PAS.0b013e31817ec2e6 18830121
53. N Theou S Gil A Devocelle C Julie A Lavergne-Slove A Beauchet P Callard R Farinotti A Le Cesne A Lemoine L Faivre-Bonhomme, et al. 2005 Multidrug resistance proteins in gastrointestinal stromal tumors: site-dependent expression and initial response to imatinib Clin Cancer Res 11 21 7593 7598 1:CAS:528:DC%2BD2MXhtF2is7bP 10.1158/1078-0432.CCR-05-0710 16278376
54. H Burger H van Tol AW Boersma M Brok EA Wiemer G Stoter K Nooter 2004 Imatinib mesylate (STI571) is a substrate for the breast cancer resistance protein (BCRP)/ABCG2 drug pump Blood 104 9 2940 2942 1:CAS:528: DC%2BD2cXpslKju7s%3D 10.1182/blood-2004-04-1398 15251980
55. D Mahadevan L Cooke C Riley R Swart B Simons K Della Croce L Wisner M Iorio K Shakalya H Garewal R Nagle, et al. 2007 A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors Oncogene 26 27 3909 3919 1:CAS:528:DC%2BD2sXmtFeqsrY%3D 10.1038/sj.onc.1210173 17325667
56. K Sakurama K Noma M Takaoka Y Tomono N Watanabe S Hatakeyama O Ohmori S Hirota T Motoki Y Shirakawa T Yamatsuji, et al. 2009 Inhibition of focal adhesion kinase as a potential therapeutic strategy for imatinib-resistant gastrointestinal stromal tumor Mol Cancer Ther 8 1 127 134 1:CAS:528: DC%2BD1MXjvFSmsw%3D%3D 10.1158/1535-7163.MCT-08-0884 19139121
57. T Muhlenberg Y Zhang AJ Wagner F Grabellus J Bradner G Taeger H Lang T Taguchi M Schuler JA Fletcher S Bauer 2009 Inhibitors of deacetylases suppress oncogenic KIT signaling, acetylate HSP90, and induce apoptosis in gastrointestinal stromal tumors Cancer Res 69 17 6941 6950 10.1158/0008-5472. CAN-08-4004 19706776
58. Demetri GD, Oosterom ATv, Blackstein M, Garrett C, Shah M, Heinrich M, McArthur G, Judson I, Baum CM, Casali PG (2005) Phase 3, multicenter, randomized, double-blind, placebo-controlled trial of SU11248 in patients (pts) following failure of imatinib for metastatic GIST. Am Soc Clin Oncol 24:138. (Abstract 4000)
59. MC Heinrich RG Maki CL Corless CR Antonescu A Harlow D Griffith A Town A McKinley WB Ou JA Fletcher CD Fletcher, et al. 2008 Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor J Clin Oncol 26 33 5352 5359 1:CAS:528:DC%2BD1MXhslCmtQ%3D%3D 10.1200/JCO.2007.15.7461 18955458
60. H Prenen J Cools N Mentens C Folens R Sciot P Schoffski A Van Oosterom P Marynen M Debiec-Rychter 2006 Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate Clin Cancer Res 12 8 2622 2627 1:CAS:528:DC%2BD28XjvVaksrg%3D 10.1158/1078-0432.CCR- 05-2275 16638875
61. T Guo M Hajdu NP Agaram H Shinoda D Veach BD Clarkson RG Maki S Singer RP Dematteo P Besmer CR Antonescu 2009 Mechanisms of sunitinib resistance in gastrointestinal stromal tumors harboring KITAY502-3ins mutation: an in vitro mutagenesis screen for drug resistance Clin Cancer Res 15 22 6862 6870 1:CAS:528:DC%2BD1MXhtl2ktL3J 10.1158/1078-0432.CCR-09-1315 19861442
62. T Nishida T Takahashi A Nishitani T Doi K Shirao Y Komatsu K Nakajima S Hirota 2009 Sunitinib-resistant gastrointestinal stromal tumors harbor cis-mutations in the activation loop of the KIT gene Int J Clin Oncol 14 2 143 149 1:CAS:528:DC%2BD1MXkvFeqtb4%3D 10.1007/s10147-008-0822-y 19390946
63. DiNitto JP, Deshmukh GD, Zhang Y, Jacques SL, Coli R, Worrall JW, Diehl W, English JM, Wu JC (2010) Function of activation loop tyrosine phosphorylation in the mechanism of c-Kit auto-activation and its implication in sunitinib resistance. J Biochem 147(4):601-609
64. A Petain D Kattygnarath J Azard 2008 Population pharmacokinetics and pharmacogentics of imatinib in children and adults Clin Cancer Res 14 21 7102 7109 1:CAS:528:DC%2BD1cXhtlensL7M 10.1158/1078-0432.CCR-08-0950 18981009
65. Judson I, Ma P, Peng B, Verweij J, Racine A, di Paola ED, van Glabbeke M, Dimitrijevic S, Scurr M, Dumez H, van Oosterom A (2005) Imatinib pharmacokinetics in patients with gastrointestinal stromal tumour: a retrospective population pharmacokinetic study over time. EORTC soft tissue and bone sarcoma group. Cancer Chemother Pharmacol 55(4):379-386
66. GD Demetri Y Wang E Wehrle A Racine Z Nikolova CD Blanke H Joensuu M von Mehren 2009 Imatinib plasma levels are correlated with clinical benefit in patients with unresectable/metastatic gastrointestinal stromal tumors J Clin Oncol Off J Am Soc Clin Oncol 27 19 3141 3147 1:CAS:528:DC%2BD1MXhtFWitb3K
67. S Singer BP Rubin ML Lux CJ Chen GD Demetri CD Fletcher JA Fletcher 2002 Prognostic value of KIT mutation type, mitotic activity, and histologic subtype in gastrointestinal stromal tumors J Clin Oncol 20 18 3898 3905 1:CAS:528:DC%2BD38XntVynsLo%3D 10.1200/JCO.2002.03.095 12228211
68. M Debiec-Rychter R Sciot A Le Cesne M Schlemmer P Hohenberger AT van Oosterom JY Blay S Leyvraz M Stul PG Casali J Zalcberg, et al. 2006 KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours Eur J Cancer 42 8 1093 1103 1:CAS:528:DC%2BD28Xks1ertb0%3D 10.1016/j.ejca.2006.01.030 16624552
69. M Debiec-Rychter H Dumez I Judson B Wasag J Verweij M Brown S Dimitrijevic R Sciot M Stul H Vranck M Scurr, et al. 2004 Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumours entered on phase I and II studies of the EORTC soft tissue and bone sarcoma group Eur J Cancer 40 5 689 695 1:CAS:528:DC%2BD2cXhvVOrtL8%3D 10.1016/j.ejca.2003.11.025 15010069
70. Glabbeke MMV, Owzar K, Rankin C, Simes J, Crowley J, (MetaGIST) GM-aG (2007) Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors (GIST): A meta-analyis based on 1,640 patients (pts). Am Soc Clin Oncol, Chicago
71. J McAuliffe W-L Wang G Pavan S Pricl D Yang S Chen A Lazar RE Pollock J Trent 2008 Unlucky 13? Differential sensitivity of exon 13 mutations to imatinib in GIST Mol Oncol 2 2 161 163 10.1016/j.molonc.2008.05.002 19383335
72. N Widmer LA Decosterd S Leyvraz MA Duchosal A Rosselet M Debiec-Rychter C Csajka J Biollaz T Buclin 2008 Relationship of imatinib-free plasma levels and target genotype with efficacy and tolerability Br J Cancer 98 10 1633 1640 1:CAS:528:DC%2BD1cXlvVWhsbs%3D 10.1038/sj.bjc.6604355 18475296
73. F Grimpen D Yip G McArthur P Waring D Goldstein M Loughrey V Beshay G Chong 2005 Resistance to imatinib, low-grade FDG-avidity on PET, and acquired KIT exon 17 mutation in gastrointestinal stromal tumour Lancet Oncol 6 9 724 727 1:CAS:528:DC%2BD2MXpslynsrY%3D 10.1016/S1470-2045(05)70321-1 16129374
74. T Koyama H Nimura K Kobayashi H Marushima H Odaira H Kashimura N Mitsumori K Yanaga 2006 Recurrent gastrointestinal stromal tumor (GIST) of the stomach associated with a novel c-kit mutation after imatinib treatment Gastric Cancer 9 3 235 239 10.1007/s10120-006-0368-5 16952044
75. A Gronchi M Fiore F Miselli MS Lagonigro P Coco A Messina S Pilotti PG Casali 2007 Surgery of residual disease following molecular-targeted therapy with imatinib mesylate in advanced/metastatic GIST Ann Surg 245 3 341 346 10.1097/01.sla.0000242710.36384.1b 17435538
76. KH Lim MJ Huang LT Chen TE Wang CL Liu CS Chang MC Liu RK Hsieh CY Tzen 2008 Molecular analysis of secondary kinase mutations in imatinib-resistant gastrointestinal stromal tumors Med Oncol 25 2 207 213 1:CAS:528: DC%2BD1cXotVOgtbY%3D 10.1007/s12032-007-9014-2 18488160
77. T Wakai T Kanda S Hirota A Ohashi Y Shirai K Hatakeyama 2004 Late resistance to imatinib therapy in a metastatic gastrointestinal stromal tumour is associated with a second KIT mutation Br J Cancer 90 11 2059 2061 1:CAS:528:DC%2BD2cXkt1GnsL0%3D 15150562
78. Wang CM, Huang K, Zhou Y, Du CY, Ye YW, Fu H, Zhou XY, Shi YQ (2009) Molecular mechanisms of secondary imatinib resistance in patients with gastrointestinal stromal tumors. J Cancer Res Clin Oncol
79. Tamborini E, Gabanti E, Lagonigro MS, Negri T, Pilotti S, Pierotti MA, Pricl S (2005) KIT/Val654 Ala receptor detected in one imatinib-resistant GIST patient. Cancer Res 65(3):1115. (Author reply 1115)
80. F Bertucci A Goncalves G Monges A Madroszyk J Guiramand V Moutardier T Noguchi P Dubreuil H Sobol 2006 Acquired resistance to imatinib and secondary KIT exon 13 mutation in gastrointestinal stromal tumour Oncol Rep 16 1 97 101 1:CAS:528:DC%2BD28Xntlansrk%3D 16786129
81. T Utsunomiya M Okamoto S Yano T Kameyama A Matsuyama S Kuma M Yamamoto M Fujiwara T Ishida 2008 Secondary c-kit mutation in a recurrent gastrointestinal stromal tumor under long-term treatment with imatinib mesylate: report of a case Surg Today 38 1 65 67 10.1007/s00595-007-3559-8 18085368
82. E Tamborini L Bonadiman A Greco V Albertini T Negri A Gronchi R Bertulli M Colecchia PG Casali MA Pierotti S Pilotti 2004 A new mutation in the KIT ATP pocket causes acquired resistance to imatinib in a gastrointestinal stromal tumor patient Gastroenterology 127 1 294 299 1:CAS:528:DC%2BD2cXmsVShsL8%3D 10.1053/j.gastro.2004.02.021 15236194