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 Mills, Jonas T. Johnson, Umamaheswar Duvvuri, Robert L. Ferris & 3 others Patrick Ha, Daniel E. Johnson, Jennifer R. Grandis

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)419-427
Number of pages9
JournalThe Journal of experimental medicine
Volume216
Issue number2
DOIs
StatePublished - Feb 4 2019
Externally publishedYes

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Head and Neck Neoplasms
Anti-Inflammatory Agents
Survival
Pharmaceutical Preparations
Drug Users
Mutation
Oncogenes
Dinoprostone
Heterografts
Drug Therapy
Carcinoma, squamous cell of head and neck

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Hedberg, M. L., Peyser, N. D., Bauman, J. E., Gooding, W. E., Li, H., Bhola, N. E., ... Grandis, J. R. (2019). Use of nonsteroidal anti-inflammatory drugs predicts improved patient survival for PIK3CA-altered head and neck cancer. The Journal of experimental medicine, 216(2), 419-427. https://doi.org/10.1084/jem.20181936

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

In: The Journal of experimental medicine, Vol. 216, No. 2, 04.02.2019, p. 419-427.

Research output: Contribution to journalArticle

Hedberg, ML, Peyser, ND, Bauman, JE, Gooding, WE, Li, H, Bhola, NE, Zhu, TR, Zeng, Y, Brand, TM, Kim, MO, Jordan, RCK, VandenBerg, S, Olivas, V, Bivona, TG, Chiosea, SI, Wang, L, Mills, G, Johnson, JT, Duvvuri, U, Ferris, RL, Ha, P, Johnson, DE & Grandis, JR 2019, 'Use of nonsteroidal anti-inflammatory drugs predicts improved patient survival for PIK3CA-altered head and neck cancer', The Journal of experimental medicine, vol. 216, no. 2, pp. 419-427. https://doi.org/10.1084/jem.20181936
Hedberg, Matthew L. ; Peyser, Noah D. ; Bauman, Julie E. ; Gooding, William E. ; Li, Hua ; Bhola, Neil E. ; Zhu, Tian Ran ; Zeng, Yan ; Brand, Toni M. ; Kim, Mi Ok ; Jordan, Richard C.K. ; VandenBerg, Scott ; Olivas, Victor ; Bivona, Trever G. ; Chiosea, Simion I. ; Wang, Lin ; Mills, Gordon ; Johnson, Jonas T. ; Duvvuri, Umamaheswar ; Ferris, Robert L. ; Ha, Patrick ; Johnson, Daniel E. ; Grandis, Jennifer R. / Use of nonsteroidal anti-inflammatory drugs predicts improved patient survival for PIK3CA-altered head and neck cancer. In: The Journal of experimental medicine. 2019 ; Vol. 216, No. 2. pp. 419-427.
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