Gastrointestinal stromal tumors: Molecular aspects and therapeutic implications;Aspects moléculaires et stratégies thérapeutiques des tumeurs stromales gastro-intestinales

Bulletin du Cancer

Volumn 95, Issue 1, 2008, Pages 107-116

  Italiano, Antoine ^a   Bui, Binh ^b  

^a CENTRE ANTOINE LACASSAGNE   (France)

^b INSTITUT BERGONIÉ   (France)

Author keywords

Gastro intestinal stromal tumor; GIST; KIT; Mutation; PDGFR ; Tyrosine kinase inhibitors

Indexed keywords

IMATINIB; NILOTINIB; PLACEBO; PROTEIN TYROSINE KINASE; SUNITINIB; 4 METHYL N (3 (4 METHYLIMIDAZOL 1 YL) 5 (TRIFLUOROMETHYL)PHENYL) 3 ((4 PYRIDIN 3 YLPYRIMIDIN 2 YL)AMINO)BENZAMIDE; 4-METHYL-N-(3-(4-METHYLIMIDAZOL-1-YL)-5-(TRIFLUOROMETHYL)PHENYL)-3-((4-PYRIDIN-3-YLPYRIMIDIN-2-YL)AMINO)BENZAMIDE; ANTINEOPLASTIC AGENT; BENZENESULFONIC ACID DERIVATIVE; DRUG DERIVATIVE; INDOLE DERIVATIVE; MASITINIB; MIDOSTAURIN; N (3,3 DIMETHYL 6 INDOLINYL) 2 (4 PYRIDINYLMETHYLAMINO)NICOTINAMIDE; NICOTINAMIDE; PHTHALAZINE DERIVATIVE; PIPERAZINE DERIVATIVE; PLATELET DERIVED GROWTH FACTOR ALPHA RECEPTOR; PROTEIN KINASE INHIBITOR; PYRIDINE DERIVATIVE; PYRIMIDINE DERIVATIVE; PYRROLE DERIVATIVE; SORAFENIB; STAUROSPORINE; STEM CELL FACTOR RECEPTOR; THIAZOLE DERIVATIVE; TUMOR PROTEIN; UNCLASSIFIED DRUG; VATALANIB;

ADVANCED CANCER; ANGIOGENESIS; CANCER PATIENT; CANCER SURVIVAL; CLINICAL TRIAL; DISEASE COURSE; DISEASE DURATION; DISEASE FREE SURVIVAL; GASTROINTESTINAL STROMAL TUMOR; HUMAN; MUTATION; REVIEW; DRUG ANTAGONISM; DRUG RESISTANCE; GENETICS;

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

EID: 39149103451     PISSN: 00074551     EISSN: 17696917     Source Type: Journal    
DOI: 10.1684/bdc.2008.0561     Document Type: Review

References (80)

1. Blay JY. {Targeted therapies of cancer : not lost in translation}. Bull Cancer 2006 ; 93 : 799-804.
2. Genevay M, Gengler C, Guillou L. {Detection of chromosomal abnormalities in soft tissue sarcomas : which sarcomas ? which abnormalities ? how ? why ?}. Bull Cancer 2007 : 781-92 ; (9+4).
3. Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 1998 ; 279 : 577-80.
4. Corless CL, Fletcher JA, Heinrich MC. Biology of gastrointestinal stromal tumours. J Clin Oncol 2004 ; 22 : 3813-25.
5. Lasota J, Jasinski M, Sarlomo-Rikala M, Miettinen M. Mutations in exon 11 of c-Kit occur preferentially in malignant versus benign gastrointestinal stromal tumours and do not occur in leiomyomas or leiomyosarcomas. Am J Pathol 1999 ; 154 : 53-60.
6. Rubin BP, Singer S, Tsao C, Duensing A, Lux ML, Ruiz R, et al. KIT activation is a ubiquitous feature of gastrointestinal stromal tumours. Cancer Res 2001 ; 61 : 8118-21.
7. Lux ML, Rubin BP, Biase TL, Chen CJ, Maclure T, Demetri G, et al. KIT extracellular and kinase domain mutations in gastrointestinal stromal tumours. Am J Pathol 2000 ; 156 : 791-5.
8. Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach : a clinicopathologic, immunohistochemical and molecular genetic study of 1756 cases with long-term follow-up. Am J Surg Pathol 2005 ; 29 : 52-68.
9. Wardelmann E, Losen I, Hans V, Neidt I, Speidel N, Bierhoff E, et al. Deletion of Trp-557 and Lys-558 in the juxtamembrane domain of the c-kit protooncogene is associated with metastatic behavior of gastrointestinal stromal tumors. Int J Cancer 2003 ; 106 : 887-95.
10. Martin J, Poveda J, Llombart-Bosch A, Ramos R, López-Guerrero JA, García del Muro J, et al. Deletions affecting codons 557-558 of the c-KIT gene indicate a poor prognosis in patients with completely resected gastrointestinal stromal tumors : a study by the Spanish Group for Sarcoma Research (GEIS). J Clin Oncol 2005 ; 23 : 6190-8.
11. Lasota J, Vel Dobosz AJ, Wasag B, Wozniak A, Kraszewska E, Michej W, et al. Presence of homozygous KIT exon 11 mutations is strongly associated with malignant clinical behavior in gastrointestinal stromal tumors. Lab Invest 2007 ; 87 : 1029-41.
12. Lasota J, Wozniak A, Sarlomo-Rikala M, Rys J, Kordek R, Nassar A, et al. Mutations in exons 9 and 13 of KIT gene are rare events in gastrointestinal stromal tumors : a study of 200 cases. Am J Pathol 2000 ; 157 : 1091-5.
13. Kinoshita K, Isozaki K, Hirota S, Nishida T, Chen H, Nakahara M, et al. C-kit gene mutation at exon 17 or 13 is very rare in sporadic gastrointestinal stromal tumors. J Gastroenterol Hepatol 2003 ; 18 : 147-51.
14. Antonescu CR, Sommer G, Sarran L, Tschernyavsky SJ, Riedel E, Woodruff JM, et al. Association of KIT exon 9 mutations with nongastric primary site and aggressive behavior : KIT mutation analysis and clinical correlates of 120 gastrointestinal stromal tumors. Clin Cancer Res 2003 ; 9 : 3329-37.
15. Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N, et al. PDGFRA activating mutations in gastrointestinal stromal tumours. Science 2003 ; 299 : 708-10.
16. Penzel R, Aulmann S, Moock M, Schwarzbach M, Rieker RJ, Mechtersheimer G. The location of KIT and PDGFRA gene mutations in gastrointestinal stromal tumours is site and phenotype associated. J Clin Pathol 2005 ; 58 : 634-9.
17. Kang HJ, Nam SW, Kim H, Rhee H, Kim NG, Kim H, et al. Correlation of KIT and platelet-derived growth factor receptor alpha mutations with gene activation and expression profiles in gastrointestinal stromal tumors. Oncogene 2005 ; 24 : 1066-74.
18. Agaimy A, Pelz AF, Corless CL, Wünsch PH, Heinrich MC, Hofstaedter F, et al. Epithelioid gastric stromal tumours of the antrum in young females with the Carney triad : a report of three new cases with mutational analysis and comparative genomic hybridization. Oncol Rep 2007 ; 18 : 9-15.
19. de Raedt T, Cools J, Debiec-Rychter M, Brems H, Mentens N, Sciot R. Intestinal neurofibromatosis is a subtype of familial Gist and results from a dominant activating mutation in PDGFRA. Gastroenterology 2006 ; 131 : 1907-12.
20. Gold JS, van der Zwan SM, Gönen M, Maki RG, Singer S, Brennan MF, et al. Outcome of metastatic GIST in the era before tyrosine kinase inhibitors. Ann Surg Oncol 2007 ; 14 : 134-42.
21. Joensuu H, Roberts PJ, Sarlomo-Rikala M, Andersson LC, Tervahartiala P, Tuveson D, et al. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 2001 ; 344 : 1052-6.
22. van Oosterom AT, Judson I, Verweij J, Stroobants S, Donato di Paola E, Dimitrijevic S, et al. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours : a phase I study. Lancet 2001 ; 358 : 1421-3.
23. Blanke CD, von Mehren M, Joensuu H, Roberts PJ, Eisenberg B, Heinrich M, et al. Evaluation of the safety and efficacy of an oral molecularly-targeted therapy, STI571, in patients with unresectable or metastatic gastrointestinal stromal tumors (GISTS) expressing C-KIT(CD117). Proc Am Soc Clin Oncol 2001 ; 20 ; (abstr 1).
24. von Mehren M, Blanke C, Joensuu H, Heinrich M, Roberts P, Eisenberg B, et al. High incidence of durable responses induced by imatinib mesylate (Gleevec) in patients with unresectable and metastatic gastrointestinal stromal tumors. Proc Am Soc Clin Oncol 2002 ; 21 ; (abstr 1608).
25. Rankin C, Von Mehren M, Blanke C, Benjamin R, Fletcher CD, Bramwell V, et al. Dose effect of imatinib in patients with metastatic Gist : phase III Sarcoma Group Study S0033. J Clin Oncol 2004 ; 22(suppl 14S) : 9005.
26. Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay JY, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib : randomised trial. Lancet 2004 ; 364 : 1127-34.
27. Benjamin RS, Choi H, Macapinlac HA, Burgess MA, Patel SR, Chen LL, et al. We should desist using Recist, at least in Gist. J Clin Oncol 2007 ; 25 : 1760-4.
28. Blanke CD, Demetri GD, Von Mehren M, Heinrich MC, Eisenberg BL, Fletcher J, et al. Long-term follow-up of a phase II randomized trial in advanced gastrointestinal stromal tumor patients treated with imatinib mesylate. J Clin Oncol 2006 ; 24(suppl 18S) : 9528.
29. Van Glabbeke MM, Owzar K, Rankin C, Simes J, Crowley J, GIST Meta-analysis Group. (MetaGIST). Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors : A meta-analyis based on 1,640 patients. J Clin Oncol 2007 ; 25(suppl 18S) : 10004.
30. Gastrointestinal stromal tumors : ESMO Clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol 2007 ; 18(Suppl 2) : ii27-ii29.
31. Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 2003 ; 21 : 4342-9.
32. Debiec-Rychter M, Dumez H, Judson I, Wasag B, Verweij J, Brown M, et al. 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 2004 ; 40 : 689-95.
33. Demetri GD, Benjamin RS, Blanke CD, Blay JY, Casali P, Choi H, et al. NCCN Task Force report : management of patients with gastrointestinal stromal tumor : update of the NCCN clinical practice guidelines. J Natl Compr Canc Netw 2007 ; 5(suppl 2) : S1-S29.
34. Blay JY, Landi B, Bonvalot S, Monges G, Ray-Coquard I, Duffaud F, et al. {Recommendations for the management of GIST patients}. Bull Cancer 2005 ; 92 : 907-18.
35. Debiec-Rychter M, Cools J, Dumez H, Sciot R, Stul M, Mentens N, 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 : 270-9.
36. Heinrich MC, Corless CL, Blanke CD, Demetri GD, Joensuu H, Roberts PJ, et al. Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J Clin Oncol 2006 ; 24 : 4764-74.
37. De Giorgi U. KIT mutations and imatinib dose effects in patients with gastrointestinal stromal tumors. J Clin Oncol 2007 ; 25 : 1146-7.
38. Debiec-Rychter M, Sciot R, Le Cesne A, Schlemmer M, Hohenberger P, van Oosterom AT, et al. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer 2006 ; 42 : 1093-103.
39. Zhu MJ, Ou WB, Fletcher CD, Cohen PS, Demetri GD, Fletcher JA. KIT oncoprotein interactions in gastrointestinal stromal tumors : therapeutic relevance. Oncogene 2007 ; 26 : 6386-95.
40. Tamborini E, Pricl S, Negri T, Lagonigro MS, Miselli F, Greco A, et al. Functional analyses and molecular modeling of two c-Kit mutations responsible for imatinib secondary resistance in GIST patients. Oncogene 2006 ; 25 : 6140-6.
41. Wardelmann E, Merkelbach-Bruse S, Pauls K, Thomas N, Schildhaus HU, Heinicke T, et al. Polyclonal evolution of multiple secondary KIT mutations in gastrointestinal stromal tumors under treatment with imatinib mesylate. Clin Cancer Res 2006 ; 12 : 1743-9.
42. Antonescu CR, Besmer P, Guo T, Arkun K, Hom G, Koryotowski B, et al. Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res 2005 ; 11 : 4182-90.
43. Théou N, Gil S, Devocelle A, Julié C, Lavergne-Slove A, Beauchet A, et al. Multidrug resistance proteins in gastrointestinal stromal tumors : site-dependent expression and initial response to imatinib. Clin Cancer Res 2005 ; 11 : 7593-8.
44. Mahadevan D, Cooke L, Riley C, Swatt R, Simons B, Della Croce K, et al. A novel tyrosine kinase switch is a mechanism of imatinib resistance in gastrointestinal stromal tumors. Oncogene 2007 ; 26 : 3909-19.
45. Zalcberg JR, Verweij J, Casali PG, Le Cesne A, Reichardt P, Blay JY, et al. Outcome of patients with advanced gastro-intestinal stromal tumours crossing over to a daily imatinib dose of 800 mg after progression on 400 mg. Eur J Cancer 2005 ; 41 : 1751-7.
46. Morgan A, Demetri GS, Fletcher JA, George S, Desai J, Maki RG, et al. Patients with imatinib mesylate-resistant GIST exhibit durable responses to sunitinib malate. Eur J Cancer 2005(suppl 3) : 421.
47. Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib : a randomised controlled trial. Lancet 2006 ; 368 : 1329-38.
48. Casali PG, Garrett CR, Blackstein ME, Shah M, Verweij J, McArthur G, et al. Updated results from a phase III trial of sunitinib in Gist patients for whom imatinib therapy has failed due to resistance or intolerance. J Clin Oncol 2006 ; 24(suppl 18S) : 9513.
49. Reichardt P, Kang YK, Ruka W, Seddon B, Baum CM, Demetri GD. Subpopulation analyses in a worldwide treatment-use trial of sunitinib in GIST patients with resistance or intolerance to prior imatinib therapy. J Clin Oncol 2007 ; 25(suppl 18S) : 10022.
50. Heinrich MC, Maki RG, Corless CL, Antonescu CR, Fletcher JA, Fletcher CD, et al. Sunitinib response in imatinib-resistant GIST correlates with KIT and PDGFRA mutation status. J Clin Oncol 2007 ; 24(suppl 18S) : 9502.
51. Heinrich MC, Corless CL, Liegl B, Fletcher CD, Raut CP, Donsky R, et al. Mechanisms of sunitinib malate (SU) resistance in gastrointestinal stromal tumors. J Clin Oncol 2007 ; 25(suppl 18S) : 10006.
52. Prenen H, Cools J, Mentens N, Folens C, Sciot R, Schöffski P, et al. Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate. Clin Cancer Res 2006 ; 12 : 2622-7.
53. Schittenhelm MM, Shiraga S, Schroeder A, Corbin AS, Griffith D, Lee FY, et al. Dasatinib (BMS-354825), a dual SRC/ABL kinase inhibitor, inhibits the kinase activity of wild-type, juxtamembrane, and activation loop mutant KIT isoforms associated with human malignancies. Cancer Res 2006 ; 66 : 473-81.
54. Guo T, Agaram NP, Wong GC, Hom G, D'Adamo D, Maki RG, et al. Sorafenib inhibits the imatinib-resistant KITT670I gatekeeper mutation in gastrointestinal stromal tumor. Clin Cancer Res 2007 ; 13 : 4874-81.
55. Shah NP, Tran C, Lee FY, Chen P, Norris D, Sawyers CL. Overriding imatinib resistance with a novel ABL kinase inhibitor. Science 2004 ; 305 : 399-401.
56. Evans TR, Morgan JA, van den Abbeele AD, McPherson IR, George S, Crawford D, et al. Phase I dose-escalation study of the SRC and multi-kinase inhibitor BMS-354825 in patients with GIST and other solid tumors. J Clin Oncol 2005 ; 23(suppl 16S) : 3034.
57. Kathula SK. Dasatinib in chronic myelogenous leukemia. N Engl J Med 2006 ; 355 : 1062 ; (author reply 1063-4).
58. Bui B, Blay J, Duffaud F, Hermine O, Le Cesne A. Preliminary efficacy and safety results of Masitinib administered, front line in patients with advanced GIST : a phase II study. J Clin Oncol 2007 ; 25(suppl 18S) : 10025.
59. Soria JC, Zurlo A, Blay JY, Bui BN, Massard C, Hermine O, et al. Final results of a phase I trial of masitinib (AB1010) in solid tumors. 2007 AACR annual meeting : abstract 946.
60. Benjamin R, Schöffski P, Hartmann JT, Bui BN, Duyster J, Schuetze S, et al. Initial results of a multicenter single arm phase 2 study of AMG 706, for the treatment of advanced imatinib-resitant gastrointestinal stroma tumors. 2006 ; CTOS 12th annual meeting : abstract 641.
61. Weisberg E, Manley PW, Breitenstein W, Brüggen J, Cowan-Jacob SW, Ray A, et al. Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell 2005 ; 7 : 129-41.
62. Verstovsek S, Giles FJ, Quintas-Cardama A, Manshouri T, Huynh L, Manley P, et al. Activity of AMN107, a novel aminopyrimidine tyrosine kinase inhibitor, against human FIP1L1-PDGFRα-expressing cells. Leuk Res 2006 ; 30 : 1499-505.
63. Weisberg E, Wright RD, Jiang J, Ray A, Moreno D, Manley PW, et al. Effects of PKC412, nilotinib, and imatinib against GIST-associated PDG-FRA mutants with differential imatinib sensitivity. Gastroenterology 2006 ; 131 : 1734-42.
64. Prenen H, Guetens G, de Boeck G, Debiec-Rychter M, Manley P, Schoffski P, et al. Cellular uptake of the tyrosine kinase inhibitors imatinib and AMN107 in gastrointestinal stromal tumor cell lines. Pharmacology 2006 ; 77 : 11-6.
65. Weisberg E, Catley L, Wright RD, Moreno D, Banerji L, Ray A, et al. Beneficial effects of combining nilotinib and imatinib in preclinical models of BCR-ABL+ leukemias. Blood 2007 ; 109 : 2112-20.
66. White DL, Saunders VA, Quinn SR, Manley PW, Hughes TP. Imatinib increases the intracellular concentration of nilotinib, which may explain the observed synergy between these drugs. Blood 2007 ; 109 : 3609-10.
67. Von Mehren M, Reichardt P, Casali PG, Blay J, Debiec-Rychter M, Dumez H, et al. A phase I study of nilotinib alone and in combination with imatinib in patients with imatinib-resistant gastrointestinal stromal tumors : study update. J Clin Oncol 2007 ; 25(suppl 18S) : 10023.
68. Fabbro D, Ruetz S, Bodis S, Pruschy M, Csermak K, Man A, et al. PKC412, a protein kinase inhibitor with a broad therapeutic potential. Anticancer Drug Des 2000 ; 15 : 17-28.
69. Weisberg E, Boulton C, Kelly LM, Manley P, Fabbro D, Meyer T, et al. Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitors PKC412. Cancer Cell 2002 ; 1 : 433-43.
70. Reichardt P, Pink D, Lindner T, Heinrich MC, Cohen PY, Wang Y. A phase I/II trial of the oral PKC-inhibitor PKC412 in combination with imatinib mesylate in patients with gastrointestinal stromal tumor refractory to IM. J Clin Oncol 2005 ; 23(suppl 16S) : 3016.
71. Joensuu H, De Braud F, Coco P, De Pas T, Putzu C, Spreafico C, et al. Phase II, open-label study of PTK787/ZK222584 for the treatment of metastatic gastrointestinal stromal tumors resistant to imatinib mesylate. Ann Oncol 2008 ; 19 : 173-7.
72. Wood JM, Bold G, Buchdunger E, Cozens R, Ferrari S, Frei J, et al. PTK787/ZK 222584, a novel and potent inhibitor of vascular endothelial growth factor receptor tyrosine kinases, impairs vascular endothelial growth factor-induced responses and tumor growth after oral administration. Cancer Res 2000 ; 60 : 2178-89.
73. Wilhelm SM, Carter C, Tang L, Wilkie D, McNabola A, Rong H, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 2004 ; 64 : 7099-109.
74. Guida T, Anaganti S, Provitera L, Gedrich R, Sullivan E, Wilhelm SM, et al. Sorafenib inhibits imatinib-resistant KIT and platelet-derived growth factor receptor beta gatekeeper mutants. Clin Cancer Res 2007 ; 13 : 3363-9.
75. Pan J, Quintás-Cardama A, Kantarjian HM, Akin C, Manshouri T, Lamb P, et al. EXEL-0862, a novel tyrosine kinase inhibitor, induces apoptosis in vitro and ex vivo in human mast cells expressing the KIT D816V mutation. Blood 2007 ; 109 : 315-22.
76. Demetri GD, George S, Morgan JA, Wagner A, Quigley MT, Polson K, et al. Inhibition of the heat shock protein 90 (Hsp90) chaperone with the novel agent IPI-504 to overcome resistance to tyrosine kinase inhibitors in metastatic Gist : updated results of a phase I trial. J Clin Oncol 2007 ; 25(suppl 18S) : 10024.
77. Lansiaux A, Bailly C. {Flavopiridol, a cyclin-dependent kinase inhibitor}. Bull Cancer 2000 ; 87 : 697-701.
78. Sambol EB, Ambrosini G, Geha RC, Kennealey PT, Decarolis P, O'connor R, et al. Flavopiridol targets c-KIT transcription and induces apoptosis in gastrointestinal stromal tumor cells. Cancer Res 2006 ; 66 : 5858-66.
79. 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 ; {Epub ahead of print}.
80. Monges G, Coindre JM, Scoazec J, Bouvier A, Blay J, Loria-Kanza Y, et al. Incidence of gastrointestinal stromal tumors in France : Results of the Progist survey conducted among pathologists. J Clin Oncol 2007 ; 25(suppl 18S) : 10047.