PIK3CA mutations enable targeting of a breast tumor dependency through mTOR-mediated MCL-1 translation

Grace R. Anderson; Suzanne E. Wardell; Merve Cakir; Lorin Crawford; Jim C. Leeds; Daniel P. Nussbaum; Pallavi S. Shankar; Ryan S. Soderquist; Elizabeth M. Stein; Jennifer P. Tingley; Peter S. Winter; Elizabeth K. Zieser-Misenheimer; Holly M. Alley; Alexander Yllanes; Victoria Haney; Kimberly L. Blackwell; Shannon J. McCall; Donald P. McDonnell; Kris C. Wood

doi:10.1126/scitranslmed.aae0348

Research ArticleCancer

PIK3CA mutations enable targeting of a breast tumor dependency through mTOR-mediated MCL-1 translation

Grace R. Anderson¹,
Suzanne E. Wardell¹,
Merve Cakir¹,²,
Lorin Crawford¹,³,
Jim C. Leeds¹,
Daniel P. Nussbaum¹,⁴,
Pallavi S. Shankar¹,
Ryan S. Soderquist¹,
Elizabeth M. Stein¹,
Jennifer P. Tingley¹,
Peter S. Winter¹,⁵,
Elizabeth K. Zieser-Misenheimer¹,
Holly M. Alley¹,
Alexander Yllanes¹,
Victoria Haney¹,
Kimberly L. Blackwell⁶,
Shannon J. McCall⁷,
Donald P. McDonnell¹ and
Kris C. Wood¹,*

¹Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.
²Program in Computational Biology and Bioinformatics, Duke University, Durham, NC 27708, USA.
³Department of Statistical Science, Duke University, Durham, NC 27708, USA.
⁴Department of Surgery, Duke University, Durham, NC 27710, USA.
⁵Program in Genetics and Genomics, Duke University, Durham, NC 27710, USA.
⁶Department of Medicine/Oncology, Duke University, Durham, NC 27710, USA.
⁷Department of Pathology, Duke University, Durham, NC 27710, USA.

↵*Corresponding author. Email: kris.wood{at}duke.edu

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Science Translational Medicine 14 Dec 2016:
Vol. 8, Issue 369, pp. 369ra175
DOI: 10.1126/scitranslmed.aae0348

Grace R. Anderson

Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.

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Suzanne E. Wardell

Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.

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Merve Cakir

Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.

Program in Computational Biology and Bioinformatics, Duke University, Durham, NC 27708, USA.

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Lorin Crawford

Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.

Department of Statistical Science, Duke University, Durham, NC 27708, USA.

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Jim C. Leeds

Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.

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Daniel P. Nussbaum

Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.

Department of Surgery, Duke University, Durham, NC 27710, USA.

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Pallavi S. Shankar

Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.

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Ryan S. Soderquist

Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.

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Elizabeth M. Stein

Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.

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Jennifer P. Tingley

Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.

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Peter S. Winter

Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.

Program in Genetics and Genomics, Duke University, Durham, NC 27710, USA.

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Elizabeth K. Zieser-Misenheimer

Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.

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Holly M. Alley

Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.

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Alexander Yllanes

Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.

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Victoria Haney

Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.

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Kimberly L. Blackwell

Department of Medicine/Oncology, Duke University, Durham, NC 27710, USA.

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Shannon J. McCall

Department of Pathology, Duke University, Durham, NC 27710, USA.

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Donald P. McDonnell

Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.

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Kris C. Wood

Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, USA.

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For correspondence: kris.wood@duke.edu

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PIK3CA mutations enable targeting of a breast tumor dependency through mTOR-mediated MCL-1 translation

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