دورية أكاديمية
أعرض في EDS

Overcoming EGFR G724S -mediated osimertinib resistance through unique binding characteristics of second-generation EGFR inhibitors.

التفاصيل البيبلوغرافية
العنوان: Overcoming EGFR G724S -mediated osimertinib resistance through unique binding characteristics of second-generation EGFR inhibitors.
المؤلفون: Fassunke J; Institute of Pathology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany., Müller F; Molecular Pathology, Institute of Pathology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, Weyertal 115b, 50931, Cologne, Germany., Keul M; Faculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, 44227, Dortmund, Germany., Michels S; Lung Cancer Group Cologne and Network Genomic Medicine (Lung Cancer), Department I of Internal Medicine, Center for Integrated Oncology Cologne-Bonn, University Hospital Cologne, Kerpener Str. 62, 50931, Cologne, Germany., Dammert MA; Molecular Pathology, Institute of Pathology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, Weyertal 115b, 50931, Cologne, Germany., Schmitt A; Center for Molecular Medicine Cologne, University of Cologne, Robert-Koch-Str. 21, 50931, Cologne, Germany.; Department I of Internal Medicine, University Hospital of Cologne, Weyertal 115b, 50931, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases, University of Cologne, Joseph Stelzmann Str. 26, 50931, Cologne, Germany., Plenker D; Molecular Pathology, Institute of Pathology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, Weyertal 115b, 50931, Cologne, Germany., Lategahn J; Faculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, 44227, Dortmund, Germany., Heydt C; Institute of Pathology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany., Brägelmann J; Molecular Pathology, Institute of Pathology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, Weyertal 115b, 50931, Cologne, Germany., Tumbrink HL; Molecular Pathology, Institute of Pathology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, Weyertal 115b, 50931, Cologne, Germany., Alber Y; Faculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, 44227, Dortmund, Germany., Klein S; Institute of Pathology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.; Molecular Pathology, Institute of Pathology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, Weyertal 115b, 50931, Cologne, Germany.; Else Kröner Forschungskolleg Clonal Evolution in Cancer, University Hospital Cologne, Weyertal 115b, 50931, Cologne, Germany., Heimsoeth A; Molecular Pathology, Institute of Pathology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, Weyertal 115b, 50931, Cologne, Germany., Dahmen I; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, Weyertal 115b, 50931, Cologne, Germany., Fischer RN; Lung Cancer Group Cologne and Network Genomic Medicine (Lung Cancer), Department I of Internal Medicine, Center for Integrated Oncology Cologne-Bonn, University Hospital Cologne, Kerpener Str. 62, 50931, Cologne, Germany., Scheffler M; Lung Cancer Group Cologne and Network Genomic Medicine (Lung Cancer), Department I of Internal Medicine, Center for Integrated Oncology Cologne-Bonn, University Hospital Cologne, Kerpener Str. 62, 50931, Cologne, Germany., Ihle MA; Institute of Pathology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany., Priesner V; Lung Cancer Group Cologne and Network Genomic Medicine (Lung Cancer), Department I of Internal Medicine, Center for Integrated Oncology Cologne-Bonn, University Hospital Cologne, Kerpener Str. 62, 50931, Cologne, Germany., Scheel AH; Institute of Pathology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany., Wagener S; Institute of Pathology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany., Kron A; Lung Cancer Group Cologne and Network Genomic Medicine (Lung Cancer), Department I of Internal Medicine, Center for Integrated Oncology Cologne-Bonn, University Hospital Cologne, Kerpener Str. 62, 50931, Cologne, Germany., Frank K; Section Pneumology, Clinic III of Internal Medicine, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany., Garbert K; Molecular Pathology, Institute of Pathology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, Weyertal 115b, 50931, Cologne, Germany., Persigehl T; Institute of Diagnostic and Interventional Radiology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany., Püsken M; Institute of Diagnostic and Interventional Radiology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany., Haneder S; Institute of Diagnostic and Interventional Radiology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany., Schaaf B; Hospital Dortmund gGmbH, Muensterstrasse 240, 44145, Dortmund, Germany., Rodermann E; Onkologie Rhein-Sieg, Schloßstraße 18, 53840, Troisdorf, Germany., Engel-Riedel W; Department of Pneumology, Lung Hospital Cologne Merheim, City of Cologne Municipal Hospitals, Cologne, Germany., Felip E; Oncology Department, Vall d'Hebron University Hospital, Barcelona, Spain., Smit EF; Thoracic Oncology Service, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands., Merkelbach-Bruse S; Institute of Pathology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany., Reinhardt HC; Center for Molecular Medicine Cologne, University of Cologne, Robert-Koch-Str. 21, 50931, Cologne, Germany.; Department I of Internal Medicine, University Hospital of Cologne, Weyertal 115b, 50931, Cologne, Germany.; Cologne Excellence Cluster on Cellular Stress Response in Aging-Associated Diseases, University of Cologne, Joseph Stelzmann Str. 26, 50931, Cologne, Germany., Kast SM; Faculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, 44227, Dortmund, Germany., Wolf J; Lung Cancer Group Cologne and Network Genomic Medicine (Lung Cancer), Department I of Internal Medicine, Center for Integrated Oncology Cologne-Bonn, University Hospital Cologne, Kerpener Str. 62, 50931, Cologne, Germany. juergen.wolf@uk-koeln.de., Rauh D; Faculty of Chemistry and Chemical Biology, TU Dortmund University, Otto-Hahn-Str. 4a, 44227, Dortmund, Germany. daniel.rauh@tu-dortmund.de., Büttner R; Institute of Pathology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany. reinhard.buettner@uk-koeln.de.; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, Weyertal 115b, 50931, Cologne, Germany. reinhard.buettner@uk-koeln.de.; Lung Cancer Group Cologne and Network Genomic Medicine (Lung Cancer), Department I of Internal Medicine, Center for Integrated Oncology Cologne-Bonn, University Hospital Cologne, Kerpener Str. 62, 50931, Cologne, Germany. reinhard.buettner@uk-koeln.de., Sos ML; Molecular Pathology, Institute of Pathology, University Hospital of Cologne, Kerpener Str. 62, 50937, Cologne, Germany. martin.sos@uni-koeln.de.; Department of Translational Genomics, Center of Integrated Oncology Cologne-Bonn, Medical Faculty, University of Cologne, Weyertal 115b, 50931, Cologne, Germany. martin.sos@uni-koeln.de.; Center for Molecular Medicine Cologne, University of Cologne, Robert-Koch-Str. 21, 50931, Cologne, Germany. martin.sos@uni-koeln.de.
المصدر: Nature communications [Nat Commun] 2018 Nov 07; Vol. 9 (1), pp. 4655. Date of Electronic Publication: 2018 Nov 07.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [London] : Nature Pub. Group
مواضيع طبية MeSH: Drug Resistance, Neoplasm/*drug effects , ErbB Receptors/*antagonists & inhibitors , Piperazines/*pharmacology , Protein Kinase Inhibitors/*pharmacology, Acrylamides ; Aniline Compounds ; Animals ; Cell Line, Tumor ; Disease Progression ; ErbB Receptors/chemistry ; ErbB Receptors/metabolism ; Female ; Humans ; Kinetics ; Mice ; Mice, Nude ; Mutation/genetics ; NIH 3T3 Cells ; Piperazines/chemistry ; Protein Binding/drug effects ; Protein Conformation ; Protein Kinase Inhibitors/chemistry
مستخلص: The emergence of acquired resistance against targeted drugs remains a major clinical challenge in lung adenocarcinoma patients. In a subgroup of these patients we identified an association between selection of EGFR T790M -negative but EGFR G724S -positive subclones and osimertinib resistance. We demonstrate that EGFR G724S limits the activity of third-generation EGFR inhibitors both in vitro and in vivo. Structural analyses and computational modeling indicate that EGFR G724S mutations may induce a conformation of the glycine-rich loop, which is incompatible with the binding of third-generation TKIs. Systematic inhibitor screening and in-depth kinetic profiling validate these findings and show that second-generation EGFR inhibitors retain kinase affinity and overcome EGFR G724S -mediated resistance. In the case of afatinib this profile translates into a robust reduction of colony formation and tumor growth of EGFR G724S -driven cells. Our data provide a mechanistic basis for the osimertinib-induced selection of EGFR G724S -mutant clones and a rationale to treat these patients with clinically approved second-generation EGFR inhibitors.
References: N Engl J Med. 2009 Sep 3;361(10):958-67. (PMID: 19692684)
Sci Rep. 2017 May 8;7(1):1540. (PMID: 28484248)
J Clin Oncol. 2013 Sep 20;31(27):3335-41. (PMID: 23816963)
J Am Chem Soc. 2010 Mar 31;132(12):4152-60. (PMID: 20201574)
J Biomol Screen. 2009 Sep;14(8):913-23. (PMID: 19675314)
Mol Cancer Ther. 2017 Oct;16(10):2234-2245. (PMID: 28729401)
N Engl J Med. 2010 Jun 24;362(25):2380-8. (PMID: 20573926)
Sci Transl Med. 2013 Dec 18;5(216):216ra177. (PMID: 24353160)
J Comput Chem. 2004 Jul 15;25(9):1157-74. (PMID: 15116359)
Mol Cell. 2009 Jan 16;33(1):43-52. (PMID: 19150426)
J Phys Chem B. 2008 Jul 31;112(30):9020-41. (PMID: 18593145)
Angew Chem Int Ed Engl. 2016 Aug 26;55(36):10909-12. (PMID: 27496389)
Cell Chem Biol. 2017 Nov 16;24(11):1388-1400.e7. (PMID: 28965727)
J Thorac Oncol. 2015 Jul;10(7):1049-57. (PMID: 26102443)
J Biol Chem. 1997 Jul 4;272(27):16946-54. (PMID: 9202006)
Cancer Res. 2017 Jun 1;77(11):2990-3000. (PMID: 28416483)
Cell. 1985 Jul;41(3):727-34. (PMID: 3924409)
J Struct Biol. 2015 Dec;192(3):539-544. (PMID: 26522274)
Nat Rev Drug Discov. 2011 Apr;10(4):307-17. (PMID: 21455239)
Nat Commun. 2016 Jun 10;7:11815. (PMID: 27283993)
Mol Cancer. 2014 Jun 04;13:141. (PMID: 24894453)
N Engl J Med. 2018 Jan 11;378(2):113-125. (PMID: 29151359)
J Thorac Oncol. 2017 Jul;12(7):e81-e84. (PMID: 28286242)
J Chem Theory Comput. 2015 Aug 11;11(8):3696-713. (PMID: 26574453)
Nat Struct Mol Biol. 2015 Dec;22(12):983-90. (PMID: 26551075)
Cancer Discov. 2014 Sep;4(9):1046-61. (PMID: 24893891)
Virchows Arch. 2018 May;472(5):807-814. (PMID: 29388014)
Cancer Cell. 2014 Mar 17;25(3):282-303. (PMID: 24651011)
Science. 2004 Jun 4;304(5676):1497-500. (PMID: 15118125)
Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13306-11. (PMID: 15329413)
Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20932-7. (PMID: 18093943)
J Med Chem. 2017 Mar 23;60(6):2361-2372. (PMID: 28225269)
Cell. 2012 May 11;149(4):860-70. (PMID: 22579287)
N Engl J Med. 2015 Apr 30;372(18):1689-99. (PMID: 25923549)
N Engl J Med. 2004 May 20;350(21):2129-39. (PMID: 15118073)
Eur J Cancer. 2009 Jan;45(2):228-47. (PMID: 19097774)
Cancer Res. 2010 Feb 1;70(3):868-74. (PMID: 20103621)
J Clin Oncol. 2018 Mar 20;36(9):841-849. (PMID: 28841389)
Clin Cancer Res. 2016 Oct 1;22(19):4837-4847. (PMID: 27252416)
Acta Crystallogr D Biol Crystallogr. 2007 Jan;63(Pt 1):80-93. (PMID: 17164530)
Nat Genet. 2017 Dec;49(12):1693-1704. (PMID: 29106415)
Lung Cancer. 2017 Oct;112:195-199. (PMID: 29191595)
Sci Transl Med. 2013 Oct 30;5(209):209ra153. (PMID: 24174329)
Nat Struct Mol Biol. 2008 Oct;15(10):1109-18. (PMID: 18794843)
Cancer Discov. 2014 Feb;4(2):246-57. (PMID: 24302556)
Lung Cancer. 2017 Sep;111:84-87. (PMID: 28838405)
Cancer Cell. 2002 Aug;2(2):117-25. (PMID: 12204532)
Nat Med. 2018 May;24(5):638-646. (PMID: 29686424)
J Biol Chem. 2011 May 27;286(21):18756-65. (PMID: 21454582)
Lancet Oncol. 2016 May;17(5):577-89. (PMID: 27083334)
Cancer Res. 2015 Jun 15;75(12):2489-500. (PMID: 25870145)
N Engl J Med. 2017 Feb 16;376(7):629-640. (PMID: 27959700)
Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2070-5. (PMID: 18227510)
Cell Cycle. 2006 Dec;5(23):2753-9. (PMID: 17172842)
J Chem Phys. 2006 Mar 28;124(12):124902. (PMID: 16599720)
Mol Cancer Ther. 2017 Feb;16(2):357-364. (PMID: 27913578)
J Clin Oncol. 2012 Sep 20;30(27):3417-20. (PMID: 22915655)
Nat Med. 2015 Jun;21(6):560-2. (PMID: 25939061)
J Mol Biol. 1993 Dec 5;234(3):779-815. (PMID: 8254673)
المشرفين على المادة: 0 (Acrylamides)
0 (Aniline Compounds)
0 (Piperazines)
0 (Protein Kinase Inhibitors)
3C06JJ0Z2O (osimertinib)
EC 2.7.10.1 (ErbB Receptors)
تواريخ الأحداث: Date Created: 20181109 Date Completed: 20190422 Latest Revision: 20220603
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC6220297
DOI: 10.1038/s41467-018-07078-0
PMID: 30405134
قاعدة البيانات: MEDLINE
الوصف
تدمد:2041-1723
DOI:10.1038/s41467-018-07078-0