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J Exp Med. 2019 Feb 4;216(2):419-427. doi: 10.1084/jem.20181936. Epub 2019 Jan 25.

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

Author information

1
Medical Scientist Training Program, University of Pittsburgh School of Medicine, Pittsburgh, PA.
2
Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
3
Department of Otolaryngology - Head and Neck Surgery, University of California, San Francisco, San Francisco, CA.
4
Department of Medicine - Hematology/Oncology, University of Arizona, Tucson, AZ.
5
Biostatistics Facility, University of Pittsburgh School of Medicine, Pittsburgh, PA.
6
Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA.
7
Department of Dermatology, University of California, San Francisco, San Francisco, CA.
8
Department of Pathology, University of California, San Francisco, San Francisco, CA.
9
Department of Medicine, University of California, San Francisco, San Francisco, CA.
10
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA.
11
Department of Systems Biology, University of Texas MD Anderson Cancer Center, Houston, TX.
12
Department of Otolaryngology - Head and Neck Surgery, University of California, San Francisco, San Francisco, CA jennifer.grandis@ucsf.edu.

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.

PMID:
30683736
PMCID:
PMC6363423
[Available on 2019-08-04]
DOI:
10.1084/jem.20181936

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