@article{a60fdd8f55bf4fb89223814d3eac747b,
title = "Use of nonsteroidal anti-inflammatory drugs predicts improved patient survival for PIK3CA-altered head and neck cancer",
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.",
author = "Hedberg, {Matthew L.} and Peyser, {Noah D.} and Bauman, {Julie E.} and Gooding, {William E.} and Hua Li and Bhola, {Neil E.} and Zhu, {Tian Ran} and Yan Zeng and Brand, {Toni M.} and Kim, {Mi Ok} and Jordan, {Richard C.K.} and Scott VandenBerg and Victor Olivas and Bivona, {Trever G.} and Chiosea, {Simion I.} and Lin Wang and Mills, {Gordon B.} and Johnson, {Jonas T.} and Umamaheswar Duvvuri and Ferris, {Robert L.} and Patrick Ha and Johnson, {Daniel E.} and Grandis, {Jennifer R.}",
note = "Funding Information: Research reported in this publication was supported by the National Institutes of Health (F30CA180235) and a pilot grant from the American Head and Neck Society to M.L. Hedberg; V Foundation for Cancer Research to J.E. Bauman; the National Institutes of Health (R01DE024728) to D.E. Johnson; the National Institutes of Health (R01CA098372, R01DE023685, and P50CA097190) and the American Cancer Society to J.R. Grandis; and the Department of Veterans{\textquoteright} Affairs Career Development Award Biomedical Laboratory Research & Development to U. Duvvuri. This project used the University of Pittsburgh Cancer Institute Biostatistics Facility that is supported in part by the National Institutes of Health award P30CA047904. The authors declare no competing financial interests. Publisher Copyright: {\textcopyright} 2019 Hedberg et al.",
year = "2019",
month = feb,
day = "1",
doi = "10.1084/jem.20181936",
language = "English (US)",
volume = "216",
pages = "419--427",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "2",
}