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Research ArticleCancer
The brain microenvironment mediates resistance in luminal breast cancer to PI3K inhibition through HER3 activation
- View ORCID ProfileDavid P. Kodack1,*,
- View ORCID ProfileVasileios Askoxylakis1,*,
- Gino B. Ferraro1,*,
- View ORCID ProfileQing Sheng2,†,
- Mark Badeaux1,
- Shom Goel1,‡,
- Xiaolong Qi1,§,
- View ORCID ProfileRam Shankaraiah1,
- Z. Alexander Cao2,
- View ORCID ProfileRakesh R. Ramjiawan1,
- Divya Bezwada1,
- Bhushankumar Patel1,
- View ORCID ProfileYongchul Song3,
- Carlotta Costa3,
- View ORCID ProfileKamila Naxerova1,
- View ORCID ProfileChristina S. F. Wong1,
- View ORCID ProfileJonas Kloepper1,¶,
- View ORCID ProfileRita Das2,†,
- View ORCID ProfileAngela Tam2,†,
- View ORCID ProfileJantima Tanboon4,
- View ORCID ProfileDan G. Duda1,
- View ORCID ProfileC. Ryan Miller5,
- View ORCID ProfileMarni B. Siegel6,
- Carey K. Anders7,
- View ORCID ProfileMelinda Sanders8,
- View ORCID ProfileMonica V. Estrada9,
- Robert Schlegel2,
- Carlos L. Arteaga10,
- Elena Brachtel4,
- View ORCID ProfileAlan Huang2,
- View ORCID ProfileDai Fukumura1,
- Jeffrey A. Engelman3,||,** and
- View ORCID ProfileRakesh K. Jain1,**
- 1Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
- 2Oncology Translational Medicine, Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA.
- 3Department of Medicine, MGH Cancer Center and HMS, Boston, MA 02129, USA.
- 4Department of Pathology, MGH and HMS, Boston, MA 02114, USA.
- 5Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27514, USA.
- 6Department of Genetics, University of North Carolina, Chapel Hill, NC 27514, USA.
- 7Division of Hematology Oncology, Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27514, USA.
- 8Department of Pathology, Microbiology, and Immunology, Vanderbilt-Ingram Cancer Center, Nashville, TN 37203, USA.
- 9Breast Cancer Research Program, Vanderbilt-Ingram Cancer Center, Nashville, TN 37203, USA.
- 10Departments of Medicine and Cancer Biology, Vanderbilt-Ingram Cancer Center, Nashville, TN 37203, USA.
- ↵**Corresponding author. Email: jain{at}steele.mgh.harvard.edu (R.K.J.); jeffrey.engelman{at}novartis.com (J.A.E.)
↵* These authors contributed equally to this work.
↵† Present address: Oncology Translational Research, Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA.
↵‡ Present address: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
↵§ Present address: Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, China.
↵¶ Present address: Centre Hospitalier Universitaire Vaudois, Département de Médecine Interne, CHUV-UNIL, Rue du Bugnon 46, 1011 Lausanne, Switzerland.
↵|| Present address: Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA.
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Science Translational Medicine 24 May 2017:
Vol. 9, Issue 391, eaal4682
DOI: 10.1126/scitranslmed.aal4682
Vol. 9, Issue 391, eaal4682
DOI: 10.1126/scitranslmed.aal4682
David P. Kodack
1Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
Vasileios Askoxylakis
1Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
Gino B. Ferraro
1Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
Qing Sheng
2Oncology Translational Medicine, Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA.
Mark Badeaux
1Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
Shom Goel
1Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
Xiaolong Qi
1Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
Ram Shankaraiah
1Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
Z. Alexander Cao
2Oncology Translational Medicine, Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA.
Rakesh R. Ramjiawan
1Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
Divya Bezwada
1Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
Bhushankumar Patel
1Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
Yongchul Song
3Department of Medicine, MGH Cancer Center and HMS, Boston, MA 02129, USA.
Carlotta Costa
3Department of Medicine, MGH Cancer Center and HMS, Boston, MA 02129, USA.
Kamila Naxerova
1Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
Christina S. F. Wong
1Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
Jonas Kloepper
1Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
Rita Das
2Oncology Translational Medicine, Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA.
Angela Tam
2Oncology Translational Medicine, Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA.
Jantima Tanboon
4Department of Pathology, MGH and HMS, Boston, MA 02114, USA.
Dan G. Duda
1Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
C. Ryan Miller
5Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27514, USA.
Marni B. Siegel
6Department of Genetics, University of North Carolina, Chapel Hill, NC 27514, USA.
Carey K. Anders
7Division of Hematology Oncology, Department of Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27514, USA.
Melinda Sanders
8Department of Pathology, Microbiology, and Immunology, Vanderbilt-Ingram Cancer Center, Nashville, TN 37203, USA.
Monica V. Estrada
9Breast Cancer Research Program, Vanderbilt-Ingram Cancer Center, Nashville, TN 37203, USA.
Robert Schlegel
2Oncology Translational Medicine, Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA.
Carlos L. Arteaga
10Departments of Medicine and Cancer Biology, Vanderbilt-Ingram Cancer Center, Nashville, TN 37203, USA.
Elena Brachtel
4Department of Pathology, MGH and HMS, Boston, MA 02114, USA.
Alan Huang
2Oncology Translational Medicine, Novartis Institute for Biomedical Research, Cambridge, MA 02139, USA.
Dai Fukumura
1Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
Jeffrey A. Engelman
3Department of Medicine, MGH Cancer Center and HMS, Boston, MA 02129, USA.
Rakesh K. Jain
1Edwin L. Steele Laboratory, Department of Radiation Oncology, Massachusetts General Hospital (MGH) and Harvard Medical School (HMS), Boston, MA 02114, USA.
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