1. Use of nonsteroidal anti-inflammatory drugs predicts improved patient survival for PIK3CA -altered head and neck cancer.
- Author
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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 GB, Johnson JT, Duvvuri U, Ferris RL, Ha P, Johnson DE, and Grandis JR
- Subjects
- Adult, Aged, Animals, Disease-Free Survival, Female, Humans, Male, Mice, Mice, Inbred NOD, Middle Aged, Survival Rate, Xenograft Model Antitumor Assays, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Carcinoma, Squamous Cell enzymology, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell mortality, Carcinoma, Squamous Cell therapy, Class I Phosphatidylinositol 3-Kinases genetics, Class I Phosphatidylinositol 3-Kinases metabolism, Head and Neck Neoplasms enzymology, Head and Neck Neoplasms genetics, Head and Neck Neoplasms mortality, Head and Neck Neoplasms therapy, Mutation, Neoplasm Proteins genetics, Neoplasm Proteins metabolism
- 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 PGE
2 production. These findings uncover a biologically plausible rationale to implement NSAID therapy in PIK3CA -altered HNSCC., (© 2019 Hedberg et al.)- Published
- 2019
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