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 -characterized cohort of 266 HNSCC patients and explored the mechanism in relevant preclinical models including patient-derived xenografts. Among subjects with 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 -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. mutation predicted sensitivity to NSAIDs in preclinical models in association with increased systemic PGE production. These findings uncover a biologically plausible rationale to implement NSAID therapy in -altered HNSCC.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363423 | PMC |
http://dx.doi.org/10.1084/jem.20181936 | DOI Listing |
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