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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 CK;
- VandenBerg, Scott;
- Olivas, Victor;
- Bivona, Trever G;
- Chiosea, Simion I;
- Wang, Lin;
- Mills, Gordon B;
- Johnson, Jonas T;
- Duvvuri, Umamaheswar;
- Ferris, Robert L;
- Ha, Patrick;
- Johnson, Daniel E;
- Grandis, Jennifer R
- et al.
Published Web Location
https://doi.org/10.1084/jem.20181936Abstract
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.
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