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jem Home » 2019 Archive » 4 February » 216 (2): 419
Article

Use of nonsteroidal anti-inflammatory drugs predicts improved patient survival for PIK3CA-altered head and neck cancer

View ORCID ProfileMatthew L. Hedberg, Noah D. Peyser, Julie E. Bauman, William E. Gooding, Hua Li, Neil E. Bhola, Tian Ran Zhu, Yan Zeng, Toni M. Brand, Mi-Ok Kim, View ORCID ProfileRichard C.K. Jordan, Scott VandenBerg, Victor Olivas, Trever G. Bivona, Simion I. Chiosea, Lin Wang, Gordon B. Mills, Jonas T. Johnson, Umamaheswar Duvvuri, Robert L. Ferris, Patrick Ha, Daniel E. Johnson, View ORCID ProfileJennifer R. Grandis  Correspondence email
Matthew L. Hedberg
Medical Scientist Training Program, University of Pittsburgh School of Medicine, Pittsburgh, PADepartment of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA
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  • ORCID record for Matthew L. Hedberg
Noah D. Peyser
Department of Otolaryngology – Head and Neck Surgery, University of California, San Francisco, San Francisco, CA
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Julie E. Bauman
Department of Medicine – Hematology/Oncology, University of Arizona, Tucson, AZ
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William E. Gooding
Biostatistics Facility, University of Pittsburgh School of Medicine, Pittsburgh, PA
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Hua Li
Department of Otolaryngology – Head and Neck Surgery, University of California, San Francisco, San Francisco, CA
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Neil E. Bhola
Department of Otolaryngology – Head and Neck Surgery, University of California, San Francisco, San Francisco, CA
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Tian Ran Zhu
Department of Otolaryngology – Head and Neck Surgery, University of California, San Francisco, San Francisco, CA
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Yan Zeng
Department of Otolaryngology – Head and Neck Surgery, University of California, San Francisco, San Francisco, CA
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Toni M. Brand
Department of Otolaryngology – Head and Neck Surgery, University of California, San Francisco, San Francisco, CA
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Mi-Ok Kim
Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA
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Richard C.K. Jordan
Department of Dermatology, University of California, San Francisco, San Francisco, CA
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Scott VandenBerg
Department of Pathology, University of California, San Francisco, San Francisco, CA
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Victor Olivas
Department of Medicine, University of California, San Francisco, San Francisco, CA
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Trever G. Bivona
Department of Medicine, University of California, San Francisco, San Francisco, CA
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Simion I. Chiosea
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA
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Lin Wang
Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA
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Gordon B. Mills
Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX
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Jonas T. Johnson
Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA
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Umamaheswar Duvvuri
Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA
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Robert L. Ferris
Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA
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Patrick Ha
Department of Otolaryngology – Head and Neck Surgery, University of California, San Francisco, San Francisco, CA
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Daniel E. Johnson
Department of Otolaryngology – Head and Neck Surgery, University of California, San Francisco, San Francisco, CA
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Jennifer R. Grandis
Department of Otolaryngology – Head and Neck Surgery, University of California, San Francisco, San Francisco, CA
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  • ORCID record for Jennifer R. Grandis
  • For correspondence: jennifer.grandis@ucsf.edu
DOI: 10.1084/jem.20181936 | Published January 25, 2019
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Abstract

PIK3CA is the most commonly altered oncogene in head and neck squamous cell carcinoma (HNSCC). We evaluated the impact of nonsteroidal anti-inflammatory drugs (NSAIDs) on survival in a PIK3CA-characterized cohort of 266 HNSCC patients and explored the mechanism in relevant preclinical models including patient-derived xenografts. Among subjects with PIK3CA mutations or amplification, regular NSAID use (≥6 mo) conferred markedly prolonged disease-specific survival (DSS; hazard ratio 0.23, P = 0.0032, 95% CI 0.09–0.62) and overall survival (OS; hazard ratio 0.31, P = 0.0043, 95% CI 0.14–0.69) compared with nonregular NSAID users. For PIK3CA-altered HNSCC, predicted 5-yr DSS was 72% for NSAID users and 25% for nonusers; predicted 5-yr OS was 78% for regular NSAID users and 45% for nonregular users. PIK3CA mutation predicted sensitivity to NSAIDs in preclinical models in association with increased systemic PGE2 production. These findings uncover a biologically plausible rationale to implement NSAID therapy in PIK3CA-altered HNSCC.

  • Submitted: 11 October 2018
  • Revision received 30 November 2018
  • Accepted: 20 December 2018
Creative Commons logoCreative Commons logohttp://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).

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© 2019 Hedberg et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).

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Use of nonsteroidal anti-inflammatory drugs predicts improved patient survival for PIK3CA-altered head and neck cancer
Matthew L. Hedberg, Noah D. Peyser, Julie E. Bauman, William E. Gooding, Hua Li, Neil E. Bhola, Tian Ran Zhu, Yan Zeng, Toni M. Brand, Mi-Ok Kim, Richard C.K. Jordan, Scott VandenBerg, Victor Olivas, Trever G. Bivona, Simion I. Chiosea, Lin Wang, Gordon B. Mills, Jonas T. Johnson, Umamaheswar Duvvuri, Robert L. Ferris, Patrick Ha, Daniel E. Johnson, Jennifer R. Grandis
Journal of Experimental Medicine Feb 2019, 216 (2) 419-427; DOI: 10.1084/jem.20181936

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The Journal of Experimental Medicine: 216 (2)

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February 4, 2019
Volume 216, No. 2

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