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Research Articles

PI3K Inhibition Impairs BRCA1/2 Expression and Sensitizes BRCA-Proficient Triple-Negative Breast Cancer to PARP Inhibition

Yasir H. Ibrahim, Celina García-García, Violeta Serra, Lei He, Kristine Torres-Lockhart, Aleix Prat, Pilar Anton, Patricia Cozar, Marta Guzmán, Judit Grueso, Olga Rodríguez, Maria Teresa Calvo, Claudia Aura, Orland Díez, Isabel T. Rubio, José Pérez, Jordi Rodón, Javier Cortés, Leif W. Ellisen, Maurizio Scaltriti and José Baselga
Yasir H. Ibrahim
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
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Celina García-García
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
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Violeta Serra
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
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Lei He
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
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Kristine Torres-Lockhart
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
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Aleix Prat
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
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Pilar Anton
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
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Patricia Cozar
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
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Marta Guzmán
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
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Judit Grueso
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
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Olga Rodríguez
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
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Maria Teresa Calvo
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
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Claudia Aura
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
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Orland Díez
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
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Isabel T. Rubio
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
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José Pérez
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
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Jordi Rodón
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
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Javier Cortés
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
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Leif W. Ellisen
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
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Maurizio Scaltriti
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
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José Baselga
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
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DOI: 10.1158/2159-8290.CD-11-0348 Published November 2012
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Article Information

Volume 2, Issue 11, pp. 1036-1047

DOI 
https://doi.org/10.1158/2159-8290.CD-11-0348
PubMed 
22915752

Published By 
American Association for Cancer Research
Print ISSN 
2159-8274
Online ISSN 
2159-8290
History 
  • Received December 23, 2011
  • Revision received July 23, 2012
  • Accepted July 31, 2012
  • Published first August 22, 2012.

Article Versions

  • Previous version (August 22, 2012 - 05:26).
  • Previous version (August 24, 2012 - 07:28).
  • Previous version (October 23, 2012 - 13:02).
  • Previous version (October 25, 2012 - 10:55).
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©2012 American Association for Cancer Research.

Author Information

  1. Yasir H. Ibrahim1,
  2. Celina García-García1,
  3. Violeta Serra1,
  4. Lei He6,7,
  5. Kristine Torres-Lockhart6,
  6. Aleix Prat5,
  7. Pilar Anton1,
  8. Patricia Cozar1,
  9. Marta Guzmán1,
  10. Judit Grueso1,
  11. Olga Rodríguez1,
  12. Maria Teresa Calvo1,
  13. Claudia Aura2,
  14. Orland Díez4,
  15. Isabel T. Rubio3,
  16. José Pérez4,
  17. Jordi Rodón4,
  18. Javier Cortés4,
  19. Leif W. Ellisen6,7,
  20. Maurizio Scaltriti6,7 and
  21. José Baselga1,6,7
  1. Authors' Affiliations:1Experimental Therapeutics Laboratory, 2Molecular Pathology, 3Breast Surgical Oncology, 4Medical Oncology, Vall d'Hebron Institute of Oncology (VHIO), Pg Vall d'Hebron, Barcelona, Spain; 5Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina; 6Massachusetts General Hospital Cancer Center, Massachusetts General Hospital; and 7Harvard Medical School, Boston, Massachusetts
  1. Corresponding Authors:
    José Baselga, Massachusetts General Hospital Cancer Center, 10 North Grove Street, LRH-1, Boston, MA 02114. Phone: 617-726-2408; Fax: 617-643-9686; E-mail: jbaselga{at}partners.org; and Maurizio Scaltriti, Massachusetts General Hospital Cancer Center, Harvard Medical School, CNY 149, 13th Street, Charlestown, MA 02129. Phone: 617-643-8239; Fax: 617-724-7298; E-mail: mscaltriti{at}partners.org
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Cancer Discovery: 2 (11)
November 2012
Volume 2, Issue 11
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PI3K Inhibition Impairs BRCA1/2 Expression and Sensitizes BRCA-Proficient Triple-Negative Breast Cancer to PARP Inhibition
Yasir H. Ibrahim, Celina García-García, Violeta Serra, Lei He, Kristine Torres-Lockhart, Aleix Prat, Pilar Anton, Patricia Cozar, Marta Guzmán, Judit Grueso, Olga Rodríguez, Maria Teresa Calvo, Claudia Aura, Orland Díez, Isabel T. Rubio, José Pérez, Jordi Rodón, Javier Cortés, Leif W. Ellisen, Maurizio Scaltriti and José Baselga
Cancer Discov November 1 2012 (2) (11) 1036-1047; DOI: 10.1158/2159-8290.CD-11-0348

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PI3K Inhibition Impairs BRCA1/2 Expression and Sensitizes BRCA-Proficient Triple-Negative Breast Cancer to PARP Inhibition
Yasir H. Ibrahim, Celina García-García, Violeta Serra, Lei He, Kristine Torres-Lockhart, Aleix Prat, Pilar Anton, Patricia Cozar, Marta Guzmán, Judit Grueso, Olga Rodríguez, Maria Teresa Calvo, Claudia Aura, Orland Díez, Isabel T. Rubio, José Pérez, Jordi Rodón, Javier Cortés, Leif W. Ellisen, Maurizio Scaltriti and José Baselga
Cancer Discov November 1 2012 (2) (11) 1036-1047; DOI: 10.1158/2159-8290.CD-11-0348
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