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ResearchIn-Press PreviewCell biologyOncology Open Access | 10.1172/JCI180927

USP10/GSK3B-mediated inhibition of PTEN drives resistance to PI3K inhibitors in breast cancer

Nishi Kumari,1 Sarah CE. Wright,2 Christopher M. Witham,2 Laia Monserrat,3 Marta Palafox,3 John Lalith Charles Richard,1 Carlotta Costa,4 Moshe Elkabets,5 Mark Agostino,2 Theresa Klemm,6 Melissa K. Eccles,2 Alexandra Garnham,7 Ting Wu,8 Jonas A. Nilsson,8 Nikita Walz,2 Veena Venugopal,1 Anthony Cerra,9 Natali Vasilevski,2 Stephanie C. Bridgeman,2 Sona Bassi,2 Azad Saei,1 Moutaz Helal,10 Philipp Neundorf,10 Angela Riedel,10 Mathias Rosenfeldt,10 Jespal Gill,12 Nikolett Pahor,13 Oliver Hartmann,13 Jacky Chung,14 Sachdev S. Sidhu,14 Nina Moderau,15 Sudhakar Jha,1 Jordi Rodon,17 Markus E. Diefenbacher,13 David Komander,19 Violeta Serra,20 and Pieter Eichhorn21

1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

Find articles by Kumari, N. in: PubMed | Google Scholar

1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

Find articles by Wright, S. in: PubMed | Google Scholar

1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

Find articles by Witham, C. in: PubMed | Google Scholar

1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

Find articles by Monserrat, L. in: PubMed | Google Scholar

1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

Find articles by Palafox, M. in: PubMed | Google Scholar

1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

Find articles by Charles Richard, J. in: PubMed | Google Scholar |

1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

Find articles by Costa, C. in: PubMed | Google Scholar

1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

Find articles by Elkabets, M. in: PubMed | Google Scholar

1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

Find articles by Agostino, M. in: PubMed | Google Scholar

1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

Find articles by Klemm, T. in: PubMed | Google Scholar

1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

Find articles by Eccles, M. in: PubMed | Google Scholar

1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

Find articles by Garnham, A. in: PubMed | Google Scholar |

1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

Find articles by Wu, T. in: PubMed | Google Scholar

1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

Find articles by Nilsson, J. in: PubMed | Google Scholar

1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

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1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

Find articles by Venugopal, V. in: PubMed | Google Scholar

1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

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1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

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1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

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1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

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1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

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1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

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1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

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1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

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1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

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1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

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1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

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1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

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1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

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1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

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1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

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1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

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1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

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1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

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1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

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1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

Find articles by Serra, V. in: PubMed | Google Scholar |

1Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

2Health Sciences, Curtin University, Bentley, Australia

3Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

4Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, United States of America

5The Shraga Segal Department of Microbiology, Immunology, and Genetics, Ben-Gurion University of the Negev, Beer-sheva, Israel

6The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

7Department of Medical Biology, The University of Melbourne, Parkville, Australia

8Harry Perkins Institute of Medical Research, University of Western Australia, Perth, Australia

9Health Sciences, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

10Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Australia

11Mildred Scheel Early Career Centre, University Hospital Würzburg, Würzburg, Germany

12Anatomical Pathology, Western Diagnostics, Murdoch, Australia

13Institute of Lung Health and Immunity, Helmholtz Center Munich, Munich, Germany

14School of Pharmacy, University of Waterloo, Kitchener, Canada

15Department of Surgery and Cancer, Imperial College London, London, United Kingdom

16Cancer Science Institute of Singapore, National University of Singapore, Singapore, United States of America

17Investigational Cancer Therapeutics Department, MD Anderson Cancer Center, Houston, United States of America

18Institute of Lung Health and Immunity, Helmholtz Center Munich, Würzburg, Germany

19Ubiquitin Signalling, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia

20Experimental Therapeutics Group, Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain

21Faculty of Health Sciences, Curtin University, Bentley, Australia

Find articles by Eichhorn, P. in: PubMed | Google Scholar

Published September 24, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI180927.
Copyright © 2025, Kumari et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published September 24, 2025 - Version history
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Abstract

Activating mutations in PIK3CA, the gene encoding the catalytic p110-alpha subunit of PI3K, are some of the most frequent genomic alterations in breast cancer. Alpelisib, a small-molecule inhibitor that targets p110-alpha, is a recommended drug for patients with PIK3CA-mutant advanced breast cancer. However, clinical success for PI3K inhibitors has been limited by their narrow therapeutic window. The lipid phosphatase PTEN is a potent tumour suppressor and a major negative regulator of the PI3K pathway. Unsurprisingly, inactivating mutations in PTEN correlate with tumour progression and resistance to PI3K inhibition due to persistent PI3K signalling. Here we demonstrate that PI3K inhibition leads rapidly to the inactivation of PTEN. Using a functional genetic screen we show that this effect is mediated by a USP10-GSK3-B signalling axis, in which USP10 stabilizes GSK3-B resulting in GSK3-B-mediated phosphorylation of the C-terminal tail of PTEN. This phosphorylation inhibits PTEN dimerization and thus prevents its activation. Downregulation of GSK3-B or USP10 re-sensitizes PI3K inhibitor resistant breast cancer models and patient derived organoids to PI3K inhibition and induces tumour regression. Our study establishes that enhancing PTEN activity is a new strategy to treat PIK3CA mutant tumours and provides a strong rationale for pursuing USP10 inhibitors in the clinic.

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