Synergistic action of the MCL-1 inhibitor S63845 with current therapies in preclinical models of triple-negative and HER2-amplified breast cancer

Delphine Merino; James R. Whittle; François Vaillant; Antonin Serrano; Jia-Nan Gong; Goknur Giner; Ana Leticia Maragno; Maïa Chanrion; Emilie Schneider; Bhupinder Pal; Xiang Li; Grant Dewson; Julius Gräsel; Kevin Liu; Najoua Lalaoui; David Segal; Marco J. Herold; David C. S. Huang; Gordon K. Smyth; Olivier Geneste; Guillaume Lessene; Jane E. Visvader; Geoffrey J. Lindeman

doi:10.1126/scitranslmed.aam7049

Research ArticleCancer

Synergistic action of the MCL-1 inhibitor S63845 with current therapies in preclinical models of triple-negative and HER2-amplified breast cancer

View ORCID ProfileDelphine Merino¹,²,*,
View ORCID ProfileJames R. Whittle¹,²,³,*,
View ORCID ProfileFrançois Vaillant¹,²,*,
Antonin Serrano¹,²,
View ORCID ProfileJia-Nan Gong²,⁴,
Goknur Giner²,⁵,
Ana Leticia Maragno⁶,
Maïa Chanrion⁶,
Emilie Schneider⁶,
Bhupinder Pal¹,²,
Xiang Li²,⁷,
Grant Dewson²,⁷,
Julius Gräsel¹,²,
Kevin Liu¹,²,
View ORCID ProfileNajoua Lalaoui²,⁷,
David Segal²,⁴,
Marco J. Herold²,⁸,
View ORCID ProfileDavid C. S. Huang²,⁴,
View ORCID ProfileGordon K. Smyth⁵,⁹,
Olivier Geneste⁶,
View ORCID ProfileGuillaume Lessene²,¹⁰,¹¹,
View ORCID ProfileJane E. Visvader¹,²,† and
Geoffrey J. Lindeman¹,³,¹²,¹³,†

¹ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
²Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.
³Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.
⁴Cancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
⁵Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
⁶Institut de Recherches Servier Oncology R&D Unit, Croissy Sur Seine 78290, France.
⁷Cell Signalling and Cell Death Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
⁸Molecular Genetics of Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
⁹School of Mathematics and Statistics, University of Melbourne, Parkville, Victoria 3010, Australia.
¹⁰Chemical Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
¹¹Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria 3010, Australia.
¹²Department of Medicine, University of Melbourne, Parkville, Victoria 3010, Australia.
¹³Parkville Familial Cancer Centre, Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Parkville, Victoria 3050, Australia.

↵†Corresponding author. Email: visvader{at}wehi.edu.au (J.E.V.); lindeman{at}wehi.edu.au (G.J.L.)

↵* These authors contributed equally to this work.

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Science Translational Medicine 02 Aug 2017:
Vol. 9, Issue 401, eaam7049
DOI: 10.1126/scitranslmed.aam7049

Delphine Merino

1ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

2Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.

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ORCID record for Delphine Merino

James R. Whittle

1ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

2Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.

3Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.

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François Vaillant

1ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

2Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.

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Antonin Serrano

1ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

2Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.

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Jia-Nan Gong

2Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.

4Cancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

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Goknur Giner

2Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.

5Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

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Ana Leticia Maragno

6Institut de Recherches Servier Oncology R&D Unit, Croissy Sur Seine 78290, France.

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Maïa Chanrion

6Institut de Recherches Servier Oncology R&D Unit, Croissy Sur Seine 78290, France.

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Emilie Schneider

6Institut de Recherches Servier Oncology R&D Unit, Croissy Sur Seine 78290, France.

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Bhupinder Pal

1ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

2Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.

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Xiang Li

2Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.

7Cell Signalling and Cell Death Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

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Grant Dewson

2Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.

7Cell Signalling and Cell Death Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

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Julius Gräsel

1ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

2Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.

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Kevin Liu

1ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

2Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.

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Najoua Lalaoui

2Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.

7Cell Signalling and Cell Death Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

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David Segal

2Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.

4Cancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

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Marco J. Herold

2Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.

8Molecular Genetics of Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

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David C. S. Huang

2Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.

4Cancer and Haematology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

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Gordon K. Smyth

5Bioinformatics Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

9School of Mathematics and Statistics, University of Melbourne, Parkville, Victoria 3010, Australia.

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Olivier Geneste

6Institut de Recherches Servier Oncology R&D Unit, Croissy Sur Seine 78290, France.

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Guillaume Lessene

2Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.

10Chemical Biology Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

11Department of Pharmacology and Therapeutics, University of Melbourne, Parkville, Victoria 3010, Australia.

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Jane E. Visvader

1ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

2Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia.

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For correspondence: visvader@wehi.edu.au lindeman@wehi.edu.au

Geoffrey J. Lindeman

1ACRF Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.

3Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.

12Department of Medicine, University of Melbourne, Parkville, Victoria 3010, Australia.

13Parkville Familial Cancer Centre, Royal Melbourne Hospital and Peter MacCallum Cancer Centre, Parkville, Victoria 3050, Australia.

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For correspondence: visvader@wehi.edu.au lindeman@wehi.edu.au

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Synergistic action of the MCL-1 inhibitor S63845 with current therapies in preclinical models of triple-negative and HER2-amplified breast cancer

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