Nature Communications (Nov 2018)
Overcoming EGFR G724S-mediated osimertinib resistance through unique binding characteristics of second-generation EGFR inhibitors
- Jana Fassunke,
- Fabienne Müller,
- Marina Keul,
- Sebastian Michels,
- Marcel A. Dammert,
- Anna Schmitt,
- Dennis Plenker,
- Jonas Lategahn,
- Carina Heydt,
- Johannes Brägelmann,
- Hannah L. Tumbrink,
- Yannic Alber,
- Sebastian Klein,
- Alena Heimsoeth,
- Ilona Dahmen,
- Rieke N. Fischer,
- Matthias Scheffler,
- Michaela A. Ihle,
- Vanessa Priesner,
- Andreas H. Scheel,
- Svenja Wagener,
- Anna Kron,
- Konrad Frank,
- Katia Garbert,
- Thorsten Persigehl,
- Michael Püsken,
- Stefan Haneder,
- Bernhard Schaaf,
- Ernst Rodermann,
- Walburga Engel-Riedel,
- Enriqueta Felip,
- Egbert F. Smit,
- Sabine Merkelbach-Bruse,
- H. Christian Reinhardt,
- Stefan M. Kast,
- Jürgen Wolf,
- Daniel Rauh,
- Reinhard Büttner,
- Martin L. Sos
Affiliations
- Jana Fassunke
- Institute of Pathology, University Hospital of Cologne
- Fabienne Müller
- Molecular Pathology, Institute of Pathology, University Hospital of Cologne
- Marina Keul
- Faculty of Chemistry and Chemical Biology, TU Dortmund University
- Sebastian Michels
- Lung Cancer Group Cologne and Network Genomic Medicine (Lung Cancer), Department I of Internal Medicine, Center for Integrated Oncology Cologne-Bonn, University Hospital Cologne
- Marcel A. Dammert
- Molecular Pathology, Institute of Pathology, University Hospital of Cologne
- Anna Schmitt
- Center for Molecular Medicine Cologne, University of Cologne
- Dennis Plenker
- Molecular Pathology, Institute of Pathology, University Hospital of Cologne
- Jonas Lategahn
- Faculty of Chemistry and Chemical Biology, TU Dortmund University
- Carina Heydt
- Institute of Pathology, University Hospital of Cologne
- Johannes Brägelmann
- Molecular Pathology, Institute of Pathology, University Hospital of Cologne
- Hannah L. Tumbrink
- Molecular Pathology, Institute of Pathology, University Hospital of Cologne
- Yannic Alber
- Faculty of Chemistry and Chemical Biology, TU Dortmund University
- Sebastian Klein
- Institute of Pathology, University Hospital of Cologne
- Alena Heimsoeth
- Molecular Pathology, Institute of Pathology, University Hospital of Cologne
- Ilona Dahmen
- Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne
- Rieke N. Fischer
- Lung Cancer Group Cologne and Network Genomic Medicine (Lung Cancer), Department I of Internal Medicine, Center for Integrated Oncology Cologne-Bonn, University Hospital Cologne
- Matthias Scheffler
- Lung Cancer Group Cologne and Network Genomic Medicine (Lung Cancer), Department I of Internal Medicine, Center for Integrated Oncology Cologne-Bonn, University Hospital Cologne
- Michaela A. Ihle
- Institute of Pathology, University Hospital of Cologne
- Vanessa Priesner
- Lung Cancer Group Cologne and Network Genomic Medicine (Lung Cancer), Department I of Internal Medicine, Center for Integrated Oncology Cologne-Bonn, University Hospital Cologne
- Andreas H. Scheel
- Institute of Pathology, University Hospital of Cologne
- Svenja Wagener
- Institute of Pathology, University Hospital of Cologne
- Anna Kron
- Lung Cancer Group Cologne and Network Genomic Medicine (Lung Cancer), Department I of Internal Medicine, Center for Integrated Oncology Cologne-Bonn, University Hospital Cologne
- Konrad Frank
- Section Pneumology, Clinic III of Internal Medicine, University Hospital of Cologne
- Katia Garbert
- Molecular Pathology, Institute of Pathology, University Hospital of Cologne
- Thorsten Persigehl
- Institute of Diagnostic and Interventional Radiology, University Hospital of Cologne
- Michael Püsken
- Institute of Diagnostic and Interventional Radiology, University Hospital of Cologne
- Stefan Haneder
- Institute of Diagnostic and Interventional Radiology, University Hospital of Cologne
- Bernhard Schaaf
- Hospital Dortmund gGmbH
- Ernst Rodermann
- Onkologie Rhein-Sieg
- Walburga Engel-Riedel
- Department of Pneumology, Lung Hospital Cologne Merheim, City of Cologne Municipal Hospitals
- Enriqueta Felip
- Oncology Department, Vall d’Hebron University Hospital
- Egbert F. Smit
- Thoracic Oncology Service, Netherlands Cancer Institute
- Sabine Merkelbach-Bruse
- Institute of Pathology, University Hospital of Cologne
- H. Christian Reinhardt
- Center for Molecular Medicine Cologne, University of Cologne
- Stefan M. Kast
- Faculty of Chemistry and Chemical Biology, TU Dortmund University
- Jürgen Wolf
- Lung Cancer Group Cologne and Network Genomic Medicine (Lung Cancer), Department I of Internal Medicine, Center for Integrated Oncology Cologne-Bonn, University Hospital Cologne
- Daniel Rauh
- Faculty of Chemistry and Chemical Biology, TU Dortmund University
- Reinhard Büttner
- Institute of Pathology, University Hospital of Cologne
- Martin L. Sos
- Molecular Pathology, Institute of Pathology, University Hospital of Cologne
- DOI
- https://doi.org/10.1038/s41467-018-07078-0
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 13
Abstract
Acquired resistance to targeted drugs remains a major clinical challenge in lung adenocarcinoma patients. Here, the authors show how the acquired EGFR G724S mutation induces resistance to third-generation EGFR inhibitors and why the mutant kinase remains susceptible to second-generation inhibitors.
