Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants
作者： Maria Debiec-Rychter , Jan Cools , Herlinde Dumez , Raf Sciot , Michel Stul
DOI: 10.1053/J.GASTRO.2004.11.020
关键词:
摘要: Background & Aims: Resistance is a major challenge in the treatment of patients with gastrointestinal stromal tumors (GISTs). We investigated mechanisms resistance progressive GISTs primary KIT mutations and efficacy kinase inhibitor PKC412 for inhibition imatinib-resistant mutants. Methods: performed cytogenetic analysis screened PDGFRA domains 26 resistant GISTs. autophosphorylation status was assessed by Western immunoblotting. Imatinib-resistant GIST cells Ba/F3 expressing these mutant proteins were tested sensitivity to imatinib PKC412. Results: Six distinct secondary detected 12 tumors, V654A T670I found be recurrent. One tumor showed acquired PDGFRA-D842V mutation. Amplification or KIT/PDGFRA 2 patients. Eight 10 available phosphorylated KIT. Two remaining lost protein expression. carrying KIT-del557-558/T670I KIT-InsAY502-503/V654A imatinib, while significantly inhibited autophosporylation KIT-T670I mutants confirmed using cells. Conclusions: This study shows high frequency domain defines genomic amplification as an alternative cause drug. In subset patients, cancer their dependence on targeted tyrosine kinase. Our findings show KIT-V654A
gastrojournal.org
core.ac.uk
elsevier.com
sci-hub.se 参考文章(27)
Urs Regenass, Elisabeth Andrejauskas-Buchdunger, Differential inhibition of the epidermal growth factor-, platelet-derived growth factor-, and protein kinase C-mediated signal transduction pathways by the staurosporine derivative CGP 41251 Cancer Research. ,vol. 52, pp. 5353- 5358 ,(1992)
Elena Tamborini, Lorena Bonadiman, Angela Greco, Veronica Albertini, Tiziana Negri, Alessandro Gronchi, Rossella Bertulli, Maurizio Colecchia, Paolo G. Casali, Marco A. Pierotti, Silvana Pilotti, A new mutation in the KIT ATP pocket causes acquired resistance to imatinib in a gastrointestinal stromal tumor patient. Gastroenterology. ,vol. 127, pp. 294- 299 ,(2004) , 10.1053/J.GASTRO.2004.02.021
Maria Debiec-Rychter, Bartosz Wasag, Michel Stul, Ivo De Wever, Allan Van Oosterom, Anne Hagemeijer, Raf Sciot, Gastrointestinal stromal tumours (GISTs) negative for KIT (CD117 antigen) immunoreactivity The Journal of Pathology. ,vol. 202, pp. 430- 438 ,(2004) , 10.1002/PATH.1546
Ellen Weisberg, Christina Boulton, Louise M Kelly, Paul Manley, Doriano Fabbro, Thomas Meyer, D.Gary Gilliland, James D Griffin, Inhibition of mutant FLT3 receptors in leukemia cells by the small molecule tyrosine kinase inhibitor PKC412. Cancer Cell. ,vol. 1, pp. 433- 443 ,(2002) , 10.1016/S1535-6108(02)00069-7
Kathleen Kemmer, Christopher L. Corless, Jonathan A. Fletcher, Laura McGreevey, Andrea Haley, Diana Griffith, Oscar W. Cummings, Cecily Wait, Ajia Town, Michael C. Heinrich, KIT mutations are common in testicular seminomas. American Journal of Pathology. ,vol. 164, pp. 305- 313 ,(2004) , 10.1016/S0002-9440(10)63120-3
B.Jack Longley, Maria Jose Reguera, Yongsheng Ma, Classes of c-KIT activating mutations: proposed mechanisms of action and implications for disease classification and therapy. Leukemia Research. ,vol. 25, pp. 571- 576 ,(2001) , 10.1016/S0145-2126(01)00028-5
Allan T van Oosterom, Ian Judson, Jaap Verweij, Sigrid Stroobants, Eugenio Donato di Paola, Sasa Dimitrijevic, Marc Martens, Andrew Webb, Raf Sciot, Martine Van Glabbeke, Sandra Silberman, Ole S Nielsen, Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. The Lancet. ,vol. 358, pp. 1421- 1423 ,(2001) , 10.1016/S0140-6736(01)06535-7
Mercedes E Gorre, Mansoor Mohammed, Katharine Ellwood, Nicholas Hsu, Ron Paquette, P Nagesh Rao, Charles L Sawyers, Clinical Resistance to STI-571 Cancer Therapy Caused by BCR-ABL Gene Mutation or Amplification Science. ,vol. 293, pp. 876- 880 ,(2001) , 10.1126/SCIENCE.1062538
Jan Cools, Daniel J. DeAngelo, Jason Gotlib, Elizabeth H. Stover, Robert D. Legare, Jorges Cortes, Jeffrey Kutok, Jennifer Clark, Ilene Galinsky, James D. Griffin, Nicholas C.P. Cross, Ayalew Tefferi, James Malone, Rafeul Alam, Stanley L. Schrier, Janet Schmid, Michal Rose, Peter Vandenberghe, Gregor Verhoef, Marc Boogaerts, Iwona Wlodarska, Hagop Kantarjian, Peter Marynen, Steven E. Coutre, Richard Stone, D. Gary Gilliland, A Tyrosine Kinase Created by Fusion of thePDGFRAandFIP1L1Genes as a Therapeutic Target of Imatinib in Idiopathic Hypereosinophilic Syndrome New England Journal of Medicine. ,vol. 348, pp. 1201- 1214 ,(2003) , 10.1056/NEJMOA025217
Christopher D.M. Fletcher, Heikki Joensuu, George D. Demetri, Margaret von Mehren, Charles D. Blanke, Annick D. Van den Abbeele, Burton Eisenberg, Peter J. Roberts, Michael C. Heinrich, David A. Tuveson, Samuel Singer, Milos Janicek, Jonathan A. Fletcher, Stuart G. Silverman, Sandra L. Silberman, Renaud Capdeville, Beate Kiese, Bin Peng, Sasa Dimitrijevic, Brian J. Druker, Christopher Corless, Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. The New England Journal of Medicine. ,vol. 347, pp. 472- 480 ,(2002) , 10.1056/NEJMOA020461