Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer (original) (raw)

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Acknowledgements

The authors thank K. Shokat for assistance with structural modeling of the AXL gatekeeper mutation, W. Polkinghorn, J. Wongvipat and E. Chan for advice and technical assistance and S. Edelheit of the Case Genomics Center for technical assistance. This work was supported by the Korean Health Technology R&D Project (grant A102059 to J.C.L.), the US National Institutes of Health (K08 1K08CA154787 to T.G.B. and P01 CA129243 to M.L.), a Uniting Against Lung Cancer Research Award, a National Lung Cancer Partnership Young Investigator Award (to T.G.B.), a grant from the La Caixa Foundation (to R.R.) and an American Cancer Society Research Scholar Grant (RSG-08-303-01 to B.H.).

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Author notes

1. Zhenfeng Zhang and Jae Cheol Lee: These authors contributed equally to this work.

Authors and Affiliations

1. Department of Pathology, Case Western Reserve University School of Medicine, University Hospitals–Case Medical Center and Ireland Cancer Center, Case Comprehensive Cancer Center, Cleveland, Ohio, USA
   Zhenfeng Zhang & Alan D Levine
2. Division of Hematology/Oncology, Case Western Reserve University School of Medicine, University Hospitals–Case Medical Center and Ireland Cancer Center, Case Comprehensive Cancer Center, Cleveland, Ohio, USA
   Zhenfeng Zhang & Mohamed Abdel-Rahman
3. Division of Hematology/Oncology, Columbia University Medical Center, New York, New York, USA
   Zhenfeng Zhang, Valerie Au, Xiaoqi Wang & Balazs Halmos
4. Department of Oncology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea
   Jae Cheol Lee, Chang-Min Choi, Sang-We Kim, Dae Ho Lee & Jung-Shin Lee
5. Division of Hematology/Oncology, Helen Diller Comprehensive Cancer Center, University of California, San Francisco, California, USA
   Luping Lin, Victor Olivas & Trever G Bivona
6. Department of Genetics, Case Western Reserve University School of Medicine, University Hospitals–Case Medical Center and Ireland Cancer Center, Case Comprehensive Cancer Center, Cleveland, Ohio, USA
   Thomas LaFramboise
7. Division of Gastroenterology and Liver Disease, Case Western Reserve University School of Medicine, University Hospitals–Case Medical Center and Ireland Cancer Center, Case Comprehensive Cancer Center, Cleveland, Ohio, USA
   Alan D Levine
8. Department of Pulmonary and Critical Care Medicine, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea
   Jin Kyung Rho, Yun Jung Choi, Chang-Min Choi & Woo Sung Kim
9. Department of Pathology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul, Korea
   Se Jin Jang & Young Soo Park
10. Thoracic Medical Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
    Vincent A Miller
11. Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
    Maria Arcila & Marc Ladanyi
12. Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
    Marc Ladanyi, Philicia Moonsamy, Charles Sawyers & Trever G Bivona
13. Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut, USA
    Titus J Boggon
14. Aerodigestive Oncology Translational Research, Translational Hematology and Oncology Research (THOR), Cleveland Clinic Taussig Cancer Institute and Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio, USA
    Patrick C Ma
15. Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Barcelona, Spain
    Carlota Costa, Miquel Taron & Rafael Rosell
16. Pangaea Biotech, USP Dexeus University Institute, Barcelona, Spain
    Carlota Costa, Miquel Taron & Rafael Rosell

Authors

1. Zhenfeng Zhang
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2. Jae Cheol Lee
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3. Luping Lin
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4. Victor Olivas
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5. Valerie Au
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6. Thomas LaFramboise
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7. Mohamed Abdel-Rahman
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8. Xiaoqi Wang
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9. Alan D Levine
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10. Jin Kyung Rho
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11. Yun Jung Choi
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12. Chang-Min Choi
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13. Sang-We Kim
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14. Se Jin Jang
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15. Young Soo Park
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16. Woo Sung Kim
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17. Dae Ho Lee
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18. Jung-Shin Lee
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19. Vincent A Miller
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20. Maria Arcila
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21. Marc Ladanyi
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22. Philicia Moonsamy
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23. Charles Sawyers
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24. Titus J Boggon
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25. Patrick C Ma
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26. Carlota Costa
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27. Miquel Taron
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28. Rafael Rosell
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29. Balazs Halmos
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30. Trever G Bivona
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Contributions

Z.Z., J.C.L., L.L., V.A., T.L., M.A.-R., X.W., A.D.L., J.K.R., Y.J.C., C.-M.C., Y.S.P., S.-W.K., D.H.L., J.-S.L., P.M. and T.G.B. performed in vitro experiments. J.C.L., V.O., S.J.J., Y.S.P. and C.C. analyzed clinical specimens. M.A. and T.G.B. analyzed clinical data. P.M. and T.G.B. performed in vivo experiments. W.S.K., P.C.M., M.L., T.J.B., V.A.M., C.S., P.M., M.T., R.R., B.H. and T.G.B. analyzed in vitro and in vivo data. B.H. and T.G.B. wrote the manuscript.

Corresponding authors

Correspondence toBalazs Halmos or Trever G Bivona.

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The authors declare no competing financial interests.

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Zhang, Z., Lee, J., Lin, L. et al. Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer.Nat Genet 44, 852–860 (2012). https://doi.org/10.1038/ng.2330

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• Received: 01 March 2012
• Accepted: 31 May 2012
• Published: 01 July 2012
• Issue Date: August 2012
• DOI: https://doi.org/10.1038/ng.2330