Skip to main content
SpringerLink
Log in

Mutationsbasierter Therapiealgorithmus bei gastrointestinalen Stromatumoren

Hat die c-Kit/PDGFRA-Mutationsanalyse Einfluss auf Therapieentscheidungen?

Mutational status based therapy algorithm for gastrointestinal stroma tumors

Does c-Kit/PDGFRA mutational analysis affect treatment decisions?

  • Schwerpunkt
  • Published:
Der Gastroenterologe Aims and scope

Zusammenfassung

Bei gastrointestinalen Stromatumoren finden sich in mindestens 85% der Fälle aktivierende Mutationen der Stammzellfaktor-Rezeptortyrosinkinase (c-Kit) oder des „platelet-derived growth factor Receptor α“ (PDGFRA). Die Therapieoptionen beinhalten neben Operation und lokalen Therapieverfahren eine systemische Therapie mit Tyrosinkinaseinhibitoren wie Imatinib oder Sunitinib. Die Systemtherapie wird eingesetzt in der neoadjuvanten, adjuvanten und metastasierten Situation. Die Kenntnis des individuellen Mutationsstatus erlaubt dabei eine Vorhersage des Ansprechens auf die Primärtherapie, und kann bei Progredienz unter der Primärtherapie ein Entscheidungskriterium für die Auswahl der Zweitlinientherapie darstellen.

Abstract

Activating mutations of the stem cell factor receptor tyrosine kinase (c-Kit) or platelet-derived growth factor receptor α (PDGFRA) can be found in at least 85% of cases of gastrointestinal stromal tumors. The therapeutic options include surgery, local treatment and systemic treatment with tyrosine kinase inhibitors, such as imatinib or sunitinib. Kinase inhibitor-based treatment is used in neoadjuvant, adjuvant and metastatic settings. Knowledge of the individual mutational status allows prediction of response to first-line medical treatment and provides information which can guide selection of the appropriate second-line therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Literatur

  1. Gastrointestinal Stromal Tumor Meta-Analysis Group (MetaGIST) (2010) Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors: a meta-analysis of 1,640 patients. J Clin Oncol 28: 1247–1253

    Article  Google Scholar 

  2. Andersson J, Bumming P, Meis-Kindblom Jm et al (2006) Gastrointestinal stromal tumors with KIT exon 11 deletions are associated with poor prognosis. Gastroenterology 130: 1573–1581

    Article  PubMed  CAS  Google Scholar 

  3. Andersson J, Sjogren H, Meis-Kindblom JM et al (2002) The complexity of KIT gene mutations and chromosome rearrangements and their clinical correlation in gastrointestinal stromal (pacemaker cell) tumors. Am J Pathol 160: 15–22

    Article  PubMed  CAS  Google Scholar 

  4. NCCN Guidelines Gastrointestinal Stromal Tumors (GIST) (2011) Version 2.2011. www.nccn.org/professionals/physician_gls/f_guidelines.asp

  5. Antonescu CR, Besmer P, Guo T et al (2005) Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res 11: 4182–4190

    Article  PubMed  CAS  Google Scholar 

  6. Antonescu CR, Sommer G, Sarran L et al (2003) 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 9: 3329–3337

    PubMed  CAS  Google Scholar 

  7. Biron P, Cassier P, Fumagalli E et al (2010) Outcome of patients (pts) with PDGFRAD842V mutant gastrointestinal stromal tumor (GIST) treated with imatinib (IM) for advanced disease. J Clin Oncol: 2010 ASCO Annual Meeting, Chicago/IL

    Google Scholar 

  8. Blanke CD, Demetri GD, von Mehren M 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 Clin Oncol 26: 620–625

    Article  PubMed  CAS  Google Scholar 

  9. Blanke CD, Rankin C, Demetri GD 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 Clin Oncol 26: 626–632

    Article  PubMed  CAS  Google Scholar 

  10. Carter TA, Wodicka LM, Shah NP et al (2005) Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinases. Proc Natl Acad Sci USA 102: 11011–11016

    Article  PubMed  CAS  Google Scholar 

  11. Casali PG, Blay JY (2010) Gastrointestinal stromal tumours: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 21 (Suppl 5): v98–v102

    Article  PubMed  Google Scholar 

  12. Casali PG, Joensuu H, Broto JM et al (2010) Preliminary data of nilotinib in the first-line treatment of patients with metastatic or unresectable gastrointestinal stromal tumors (GIST). J Clin Oncol: 2010 ASCO Annual Meeting, Chicago/IL

    Google Scholar 

  13. Cauchi C, Somaiah N, Engstrom PF et al (2010) Evaluation of nilotinib (N) in advanced GIST previously treated with imatinib mesylate (IM) and sunitinib (S). J Clin Oncol: 2010 ASCO Annual Meeting, Chicago/IL

    Google Scholar 

  14. Chen Ll, Trent JC, Wu EF et al (2004) A missense mutation in KIT kinase domain 1 correlates with imatinib resistance in gastrointestinal stromal tumors. Cancer Res 64: 5913–5919

    Article  PubMed  CAS  Google Scholar 

  15. Corless C, Ballman KV, Antonescu CR et al (2010) Relation of tumor pathologic and molecular features to outcome after surgical resection of localized primary gastrointestinal stromal tumor (GIST): Results of the intergroup phase III trial ACOSOG Z9001. J Clin Oncol: 2010 ASCO Annual Meeting, Chicago/IL

    Google Scholar 

  16. Corless Cl, Barnett CM, Heinrich MC (2011) Gastrointestinal stromal tumours: origin and molecular oncology. Nat Rev Cancer 11: 865–878

    PubMed  CAS  Google Scholar 

  17. Corless Cl, Fletcher JA, Heinrich MC (2004) Biology of gastrointestinal stromal tumors. J Clin Oncol 22: 3813–3825

    Article  PubMed  CAS  Google Scholar 

  18. Corless Cl, Heinrich MC (2008) Molecular pathobiology of gastrointestinal stromal sarcomas. Annu Rev Pathol 3: 557–586

    Article  PubMed  CAS  Google Scholar 

  19. Corless Cl, Mcgreevey L, Haley A et al (2002) KIT mutations are common in incidental gastrointestinal stromal tumors one centimeter or less in size. Am J Pathol 160: 1567–1572

    Article  PubMed  CAS  Google Scholar 

  20. Corless Cl, Schroeder A, Griffith D et al (2005) PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol 23: 5357–5364

    Article  PubMed  CAS  Google Scholar 

  21. Debiec-Rychter M, Cools J, Dumez H 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: 270–279

    Article  PubMed  CAS  Google Scholar 

  22. Debiec-Rychter M, Dumez H, Judson I 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: 689–695

    Article  PubMed  CAS  Google Scholar 

  23. Debiec-Rychter M, Sciot R, Le Cesne A et al (2006) KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer 42: 1093–1103

    Article  PubMed  CAS  Google Scholar 

  24. Dematteo RP, Ballman Kv, Antonescu Cr et al (2009) Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet 373: 1097–1104

    Article  PubMed  CAS  Google Scholar 

  25. Dematteo RP, Gold JS, Saran L et al (2008) Tumor mitotic rate, size, and location independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST). Cancer 112: 608–615

    Article  PubMed  Google Scholar 

  26. Dematteo RP, Heinrich MC, El-Rifai WM et al (2002) Clinical management of gastrointestinal stromal tumors: before and after STI-571. Hum Pathol 33: 466–477

    Article  PubMed  CAS  Google Scholar 

  27. Demetri GD, Van Oosterom AT, Garrett CR et al (2006) Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 368: 1329–1338

    Article  PubMed  CAS  Google Scholar 

  28. Demetri GD, Von Mehren M, Blanke CD et al (2002) Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347: 472–480

    Article  PubMed  CAS  Google Scholar 

  29. Dewaele B, Wasag B, Cools J et al (2008) Activity of dasatinib, a dual SRC/ABL kinase inhibitor, and IPI-504, a heat shock protein 90 inhibitor, against gastrointestinal stromal tumor-associated PDGFRAD842V mutation. Clin Cancer Res 14: 5749–5758

    Article  PubMed  CAS  Google Scholar 

  30. Fletcher CD (2002) Clinicopathologic correlations in gastrointestinal stromal tumors. Hum Pathol 33: 455

    Article  PubMed  Google Scholar 

  31. George S, Von Mehren M, Heinrich Mc et al (2011) A multicenter phase II study of regorafenib in patients (pts) with advanced gastrointestinal stromal tumor (GIST), after therapy with imatinib (IM) and sunitinib (SU). J Clin Oncol: 2011 ASCO Annual Meeting, Chicago/IL

    Google Scholar 

  32. Gold JS, Gonen M, Gutierrez A et al (2009) Development and validation of a prognostic nomogram for recurrence-free survival after complete surgical resection of localised primary gastrointestinal stromal tumour: a retrospective analysis. Lancet Oncol 10: 1045–1052

    Article  PubMed  Google Scholar 

  33. Guo T, Agaram NP, Wong GC et al (2007) Sorafenib inhibits the imatinib-resistant KITT670I gatekeeper mutation in gastrointestinal stromal tumor. Clin Cancer Res 13: 4874–4881

    Article  PubMed  CAS  Google Scholar 

  34. Guo T, Hajdu M, Agaram NP et al (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: 6862–6870

    Article  PubMed  CAS  Google Scholar 

  35. Heinrich MC, Corless Cl, Blanke CD et al (2006) Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J Clin Oncol 24: 4764–4774

    Article  PubMed  CAS  Google Scholar 

  36. Heinrich MC, Corless Cl, Demetri GD et al (2003) Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 21: 4342–4349

    Article  PubMed  CAS  Google Scholar 

  37. Heinrich MC, Griffith D, Mckinley A et al (2011) The effect of crenolanib (CP-868596) on phosphorylation of the imatinib-resistant D842V PDGFRA activating mutation associated with advanced gastrointestinal stromal tumors. J Clin Oncol: 2011 ASCO Annual Meeting, Chicago/IL

    Google Scholar 

  38. Heinrich MC, Maki RG, Corless Cl 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: 5352–5359

    Article  PubMed  CAS  Google Scholar 

  39. Heinrich MC, Owzar K, Corless Cl 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 Clin Oncol 26: 5360–5367

    Article  PubMed  CAS  Google Scholar 

  40. Hirota S, Isozaki K, Moriyama Y et al (1998) Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 279: 577–580

    Article  PubMed  CAS  Google Scholar 

  41. Hirota S, Ohashi A, Nishida T et al (2003) Gain-of-function mutations of platelet-derived growth factor receptor alpha gene in gastrointestinal stromal tumors. Gastroenterology 125: 660–667

    Article  PubMed  CAS  Google Scholar 

  42. Hohenberger P, Reichardt P, Stroszczynski C et al (2003) Gastrointestinale Stromatumoren-Tumorentität und Therapie mit Imatinib. Dtsch Ärztebl 100: 1612–1618

    Google Scholar 

  43. Hostein I, Faur N, Primois C et al (2010) BRAF mutation status in gastrointestinal stromal tumors. Am J Clin Pathol 133: 141–148

    Article  PubMed  CAS  Google Scholar 

  44. Iesalnieks I, Rummele P, Dietmaier W et al (2005) Factors associated with disease progression in patients with gastrointestinal stromal tumors in the pre-imatinib era. Am J Clin Pathol 124: 740–748

    Article  PubMed  Google Scholar 

  45. Janeway KA, Kim SY, Lodish M et al (2011) Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations. Proc Natl Acad Sci USA 108: 314–318

    Article  PubMed  CAS  Google Scholar 

  46. Janeway KA, Liegl B, Harlow A et al (2007) 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 67: 9084–9088

    Article  PubMed  CAS  Google Scholar 

  47. Joensuu H (2008) Risk stratification of patients diagnosed with gastrointestinal stromal tumor. Hum Pathol 39: 1411–1419

    Article  PubMed  Google Scholar 

  48. Joensuu H, Eriksson M, Hartmann J et al (2011) Twelve versus 36 months of adjuvant imatinib (IM) as treatment of operable GIST with a high risk of recurrence: Final results of a randomized trial (SSGXVIII/AIO). J Clin Oncol: 2011 ASCO Annual Meeting, Chicago/IL

    Google Scholar 

  49. Joensuu H, Roberts PJ, Sarlomo-Rikala M et al (2001) Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 344: 1052–1056

    Article  PubMed  CAS  Google Scholar 

  50. Kindblom Lg, Remotti He, Aldenborg F et al (1998) Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol 152: 1259–1269

    PubMed  CAS  Google Scholar 

  51. Kindler Hl, Campbell NP, Wroblewski K et al (2011) Sorafenib (SOR) in patients (pts) with imatinib (IM) and sunitinib (SU)-resistant (RES) gastrointestinal stromal tumors (GIST): Final results of a University of Chicago Phase II Consortium trial. J Clin Oncol: 2011 ASCO Annual Meeting, Chicago/IL

    Google Scholar 

  52. Lasota J, Dansonka-Mieszkowska A, Sobin Lh et al (2004) A great majority of GISTs with PDGFRA mutations represent gastric tumors of low or no malignant potential. Lab Invest 84: 874–883

    Article  PubMed  CAS  Google Scholar 

  53. Lasota J, Kopczynski J, Sarlomo-Rikala M et al (2003) KIT 1530ins6 mutation defines a subset of predominantly malignant gastrointestinal stromal tumors of intestinal origin. Hum Pathol 34: 1306–1312

    Article  PubMed  CAS  Google Scholar 

  54. Lasota J, Wozniak A, Sarlomo-Rikala M et al (2000) Mutations in exons 9 and 13 of KIT gene are rare events in gastrointestinal stromal tumors. A study of 200 cases. Am J Pathol 157: 1091–1095

    Article  PubMed  CAS  Google Scholar 

  55. Liegl B, Kepten I, Le C et al (2008) Heterogeneity of kinase inhibitor resistance mechanisms in GIST. J Pathol 216: 64–74

    Article  PubMed  CAS  Google Scholar 

  56. Lux Ml, Rubin BP, Biase Tl et al (2000) KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors. Am J Pathol 156: 791–795

    Article  PubMed  CAS  Google Scholar 

  57. Ma Y, Cunningham ME, Wang X et al (1999) Inhibition of spontaneous receptor phosphorylation by residues in a putative alpha-helix in the KIT intracellular juxtamembrane region. J Biol Chem 274: 13399–13402

    Article  PubMed  CAS  Google Scholar 

  58. Martin J, Poveda A, Llombart-Bosch A et al (2005) 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 23: 6190–6198

    Article  PubMed  CAS  Google Scholar 

  59. Mcwhinney Sr, Pasini B, Stratakis Ca (2007) Familial gastrointestinal stromal tumors and germ-line mutations. N Engl J Med 357: 1054–1056

    Article  PubMed  CAS  Google Scholar 

  60. Medeiros F, Corless Cl, Duensing A et al (2004) KIT-negative gastrointestinal stromal tumors: proof of concept and therapeutic implications. Am J Surg Pathol 28: 889–894

    Article  PubMed  Google Scholar 

  61. Miettinen M, Lasota J (2006) Gastrointestinal stromal tumors: pathology and prognosis at different sites. Semin Diagn Pathol 23: 70–83

    Article  PubMed  Google Scholar 

  62. Miettinen M, Makhlouf H, Sobin Lh et al (2006) Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic, immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up. Am J Surg Pathol 30: 477–489

    Article  PubMed  Google Scholar 

  63. Montemurro M, Schoffski P, Reichardt P et al (2009) Nilotinib in the treatment of advanced gastrointestinal stromal tumours resistant to both imatinib and sunitinib. Eur J Cancer 45: 2293–2297

    Article  PubMed  CAS  Google Scholar 

  64. Olry A, Aymé S (eds) (2010) Prevalence of rare diseases: Bibliographic data; Nr. 2: Listed in order of decreasing prevalence or number of published cases. Orphanet Report Series, Paris

  65. Pantaleo MA, Nannini M, Astolfi A et al (2011) A distinct pediatric-type gastrointestinal stromal tumor in adults: potential role of succinate dehydrogenase subunit A mutations. Am J Surg Pathol 35: 1750–1752

    Article  PubMed  Google Scholar 

  66. Prenen H, Cools J, Mentens N et al (2006) Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate. Clin Cancer Res 12: 2622–2627

    Article  PubMed  CAS  Google Scholar 

  67. Reichardt P, Blay JY, Gelderblom H et al (2010) Phase III trial of nilotinib in patients with advanced gastrointestinal stromal tumor (GIST): First results from ENEST g3. J Clin Oncol: 2010 ASCO Annual Meeting, Chicago/IL

    Google Scholar 

  68. Reichardt P, Schütte J (2011) DGHO-Onkopedia Leitlinien Gastrointestinale Stromatumore (GIST). Version Juni 2011. www.dgho-onkopedia.de/onkopedia/leitlinien/gastrointestinale-stromatumore-gist

  69. Rossi S, Miceli R, Messerini L et al (2011) Natural history of imatinib-naive GISTs: a retrospective analysis of 929 cases with long-term follow-up and development of a survival nomogram based on mitotic index and size as continuous variables. Am J Surg Pathol 35: 1646–1656

    Article  PubMed  Google Scholar 

  70. Rubin Bp, Singer S, Tsao C et al (2001) KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res 61: 8118–8121

    PubMed  CAS  Google Scholar 

  71. Rutkowski P, Bylina E, Wozniak A et al (2011) Validation of the Joensuu risk criteria for primary resectable gastrointestinal stromal tumour – the impact of tumour rupture on patient outcomes. Eur J Surg Oncol 37: 890–896

    Article  PubMed  CAS  Google Scholar 

  72. Tamborini E, Bonadiman L, Greco A et al (2004) A new mutation in the KIT ATP pocket causes acquired resistance to imatinib in a gastrointestinal stromal tumor patient. Gastroenterology 127: 294–299

    Article  PubMed  CAS  Google Scholar 

  73. Taniguchi M, Nishida T, Hirota S et al (1999) Effect of c-kit mutation on prognosis of gastrointestinal stromal tumors. Cancer Res 59: 4297–4300

    PubMed  CAS  Google Scholar 

  74. Tran T, Davila JA, El-Serag HB (2005) The epidemiology of malignant gastrointestinal stromal tumors: an analysis of 1,458 cases from 1992–2000. Am J Gastroenterol 100: 162–168

    Article  PubMed  Google Scholar 

  75. Trent JC, Wathen K, Von Mehren M et al (2011) A phase II study of dasatinib for patients with imatinib-resistant gastrointestinal stromal tumor (GIST). J Clin Oncol: 2011 ASCO Annual Meeting, Chicago/IL

    Google Scholar 

  76. Tzen CY, Mau Bl (2005) Analysis of CD117-negative gastrointestinal stromal tumors. World J Gastroenterol 11: 1052–1055

    PubMed  CAS  Google Scholar 

  77. Verweij J, Casali PG, Zalcberg J et al (2004) Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet 364: 1127–1134

    Article  PubMed  CAS  Google Scholar 

  78. Von Mehren M, Heinrich MC, Joensuu H et al (2011) Follow-up results after 9 years (yrs) of the ongoing, phase II B2222 trial of imatinib mesylate (IM) in patients (pts) with metastatic or unresectable KIT + gastrointestinal stromal tumors (GIST). J Clin Oncol: 2011 ASCO Annual Meeting, Chicago/IL

    Google Scholar 

  79. Wardelmann E, Hrychyk A, Merkelbach-Bruse S et al (2004) Association of platelet-derived growth factor receptor alpha mutations with gastric primary site and epithelioid or mixed cell morphology in gastrointestinal stromal tumors. J Mol Diagn 6: 197–204

    Article  PubMed  CAS  Google Scholar 

  80. Wardelmann E, Losen I, Hans V et al (2003) 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 106: 887–895

    Article  PubMed  CAS  Google Scholar 

  81. Wardelmann E, Merkelbach-Bruse S, Pauls K et al (2006) Polyclonal evolution of multiple secondary KIT mutations in gastrointestinal stromal tumors under treatment with imatinib mesylate. Clin Cancer Res 12: 1743–1749

    Article  PubMed  CAS  Google Scholar 

  82. Wardelmann E, Thomas N, Merkelbach-Bruse S et al (2005) Acquired resistance to imatinib in gastrointestinal stromal tumours caused by multiple KIT mutations. Lancet Oncol 6: 249–251

    Article  PubMed  CAS  Google Scholar 

  83. Yuzawa S, Opatowsky Y, Zhang Z et al (2007) Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor. Cell 130: 323–334

    Article  PubMed  CAS  Google Scholar 

  84. Zalcberg JR, Verweij J, Casali PG et al (2005) 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 41: 1751–1757

    Article  PubMed  CAS  Google Scholar 

Download references

Interessenkonflikt

Der Autor gibt an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

  1. III. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Technische Universität München, Ismaningerstr. 22, 81675, München, Deutschland

    N. von Bubnoff

Authors
  1. N. von Bubnoff
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to N. von Bubnoff.

Rights and permissions

Reprints and permissions

About this article

Cite this article

von Bubnoff, N. Mutationsbasierter Therapiealgorithmus bei gastrointestinalen Stromatumoren. Gastroenterologe 7, 30–36 (2012). https://doi.org/10.1007/s11377-011-0612-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11377-011-0612-3

Schlüsselwörter

Keywords

Search

Navigation