Research ArticleCancer
Drugging the catalytically inactive state of RET kinase in RET-rearranged tumors
- View ORCID ProfileDennis Plenker1,2,*,
- View ORCID ProfileMaximilian Riedel1,2,*,
- View ORCID ProfileJohannes Brägelmann1,2,
- Marcel A. Dammert1,2,
- Rakhee Chauhan3,
- Phillip P. Knowles3,
- Carina Lorenz1,2,
- View ORCID ProfileMarina Keul4,
- Mike Bührmann4,
- View ORCID ProfileOliver Pagel5,
- Verena Tischler2,
- View ORCID ProfileAndreas H. Scheel6,
- Daniel Schütte2,
- View ORCID ProfileYanrui Song7,
- View ORCID ProfileJustina Stark4,
- Florian Mrugalla4,
- Yannic Alber4,
- André Richters4,
- Julian Engel4,
- Frauke Leenders8,
- View ORCID ProfileJohannes M. Heuckmann8,
- Jürgen Wolf9,
- Joachim Diebold10,
- Georg Pall11,
- Martin Peifer2,
- View ORCID ProfileMaarten Aerts12,13,
- Kris Gevaert12,13,
- René P. Zahedi5,
- Reinhard Buettner6,
- Kevan M. Shokat14,
- View ORCID ProfileNeil Q. McDonald3,15,
- Stefan M. Kast4,
- Oliver Gautschi10,†,
- Roman K. Thomas2,9,16,† and
- View ORCID ProfileMartin L. Sos1,2,†,‡
- 1Molecular Pathology, Institute of Pathology, Center of Integrated Oncology, University Hospital Cologne, 50937 Cologne, Germany.
- 2Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
- 3Structural Biology Laboratory, Francis Crick Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK.
- 4Faculty of Chemistry and Chemical Biology, TU Dortmund University, 44227 Dortmund, Germany.
- 5Leibniz-Institut für Analytische Wissenschaften–ISAS–e.V., Dortmund, Germany.
- 6Institute of Pathology, Center of Integrated Oncology, University Hospital Cologne, 50937 Cologne, Germany.
- 7Crown BioScience, Inc., 3375 Scott Blvd, Suite 108, Santa Clara, CA 95054, USA.
- 8NEO New Oncology GmbH, 51105 Cologne, Germany.
- 9Department of Internal Medicine, Center for Integrated Oncology Köln Bonn, University Hospital Cologne, Cologne, 50931 Cologne, Germany.
- 10Cancer Center, Lucerne Cantonal Hospital, 6000 Lucerne, Switzerland.
- 11Department of Internal Medicine 5, University Hospital Innsbruck, Haematology/Oncology, Anichstraße 35, 6020 Innsbruck, Austria.
- 12VIB-UGent Center for Medical Biotechnology, VIB, B-9000 Ghent, Belgium.
- 13Department of Biochemistry, Ghent University, B-9000 Ghent, Belgium.
- 14Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
- 15Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College, Malet Street, London WC1E 7HX, UK.
- 16German Cancer Consortium (DKTK), partner site Heidelberg, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
- ↵‡Corresponding author. Email: martin.sos{at}uni-koeln.de
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Science Translational Medicine 14 Jun 2017:
Vol. 9, Issue 394, eaah6144
DOI: 10.1126/scitranslmed.aah6144
Vol. 9, Issue 394, eaah6144
DOI: 10.1126/scitranslmed.aah6144
Dennis Plenker
1Molecular Pathology, Institute of Pathology, Center of Integrated Oncology, University Hospital Cologne, 50937 Cologne, Germany.
2Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
Maximilian Riedel
1Molecular Pathology, Institute of Pathology, Center of Integrated Oncology, University Hospital Cologne, 50937 Cologne, Germany.
2Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
Johannes Brägelmann
1Molecular Pathology, Institute of Pathology, Center of Integrated Oncology, University Hospital Cologne, 50937 Cologne, Germany.
2Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
Marcel A. Dammert
1Molecular Pathology, Institute of Pathology, Center of Integrated Oncology, University Hospital Cologne, 50937 Cologne, Germany.
2Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
Rakhee Chauhan
3Structural Biology Laboratory, Francis Crick Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK.
Phillip P. Knowles
3Structural Biology Laboratory, Francis Crick Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK.
Carina Lorenz
1Molecular Pathology, Institute of Pathology, Center of Integrated Oncology, University Hospital Cologne, 50937 Cologne, Germany.
2Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
Marina Keul
4Faculty of Chemistry and Chemical Biology, TU Dortmund University, 44227 Dortmund, Germany.
Mike Bührmann
4Faculty of Chemistry and Chemical Biology, TU Dortmund University, 44227 Dortmund, Germany.
Oliver Pagel
5Leibniz-Institut für Analytische Wissenschaften–ISAS–e.V., Dortmund, Germany.
Verena Tischler
2Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
Andreas H. Scheel
6Institute of Pathology, Center of Integrated Oncology, University Hospital Cologne, 50937 Cologne, Germany.
Daniel Schütte
2Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
Yanrui Song
7Crown BioScience, Inc., 3375 Scott Blvd, Suite 108, Santa Clara, CA 95054, USA.
Justina Stark
4Faculty of Chemistry and Chemical Biology, TU Dortmund University, 44227 Dortmund, Germany.
Florian Mrugalla
4Faculty of Chemistry and Chemical Biology, TU Dortmund University, 44227 Dortmund, Germany.
Yannic Alber
4Faculty of Chemistry and Chemical Biology, TU Dortmund University, 44227 Dortmund, Germany.
André Richters
4Faculty of Chemistry and Chemical Biology, TU Dortmund University, 44227 Dortmund, Germany.
Julian Engel
4Faculty of Chemistry and Chemical Biology, TU Dortmund University, 44227 Dortmund, Germany.
Frauke Leenders
8NEO New Oncology GmbH, 51105 Cologne, Germany.
Johannes M. Heuckmann
8NEO New Oncology GmbH, 51105 Cologne, Germany.
Jürgen Wolf
9Department of Internal Medicine, Center for Integrated Oncology Köln Bonn, University Hospital Cologne, Cologne, 50931 Cologne, Germany.
Joachim Diebold
10Cancer Center, Lucerne Cantonal Hospital, 6000 Lucerne, Switzerland.
Georg Pall
11Department of Internal Medicine 5, University Hospital Innsbruck, Haematology/Oncology, Anichstraße 35, 6020 Innsbruck, Austria.
Martin Peifer
2Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
Maarten Aerts
12VIB-UGent Center for Medical Biotechnology, VIB, B-9000 Ghent, Belgium.
13Department of Biochemistry, Ghent University, B-9000 Ghent, Belgium.
Kris Gevaert
12VIB-UGent Center for Medical Biotechnology, VIB, B-9000 Ghent, Belgium.
13Department of Biochemistry, Ghent University, B-9000 Ghent, Belgium.
René P. Zahedi
5Leibniz-Institut für Analytische Wissenschaften–ISAS–e.V., Dortmund, Germany.
Reinhard Buettner
6Institute of Pathology, Center of Integrated Oncology, University Hospital Cologne, 50937 Cologne, Germany.
Kevan M. Shokat
14Department of Cellular and Molecular Pharmacology, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
Neil Q. McDonald
3Structural Biology Laboratory, Francis Crick Institute, 44 Lincoln’s Inn Fields, London WC2A 3LY, UK.
15Institute of Structural and Molecular Biology, Department of Biological Sciences, Birkbeck College, Malet Street, London WC1E 7HX, UK.
Stefan M. Kast
4Faculty of Chemistry and Chemical Biology, TU Dortmund University, 44227 Dortmund, Germany.
Oliver Gautschi
10Cancer Center, Lucerne Cantonal Hospital, 6000 Lucerne, Switzerland.
Roman K. Thomas
2Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
9Department of Internal Medicine, Center for Integrated Oncology Köln Bonn, University Hospital Cologne, Cologne, 50931 Cologne, Germany.
16German Cancer Consortium (DKTK), partner site Heidelberg, and German Cancer Research Center (DKFZ), Heidelberg, Germany.
Martin L. Sos
1Molecular Pathology, Institute of Pathology, Center of Integrated Oncology, University Hospital Cologne, 50937 Cologne, Germany.
2Department of Translational Genomics, Center of Integrated Oncology Cologne–Bonn, Medical Faculty, University of Cologne, 50931 Cologne, Germany.
