Use of nonsteroidal anti-inflammatory drugs predicts improved patient survival for PIK3CA-altered head and neck cancer
AuthorHedberg, Matthew L
Peyser, Noah D
Bauman, Julie E
Gooding, William E
Bhola, Neil E
Zhu, Tian Ran
Brand, Toni M
Jordan, Richard C K
Bivona, Trever G
Chiosea, Simion I
Mills, Gordon B
Johnson, Jonas T
Ferris, Robert L
Johnson, Daniel E
Grandis, Jennifer R
AffiliationUniv Arizona, Dept Med Hematol Oncol
MetadataShow full item record
PublisherROCKEFELLER UNIV PRESS
CitationHedberg, M. L., Peyser, N. D., Bauman, J. E., Gooding, W. E., Li, H., Bhola, N. E., ... & Jordan, R. C. (2019). Use of nonsteroidal anti-inflammatory drugs predicts improved patient survival for PIK3CA-altered head and neck cancer. Journal of Experimental Medicine, 216(2), 419-427.
JournalJOURNAL OF EXPERIMENTAL MEDICINE
Rights© 2019 Hedberg et al.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at firstname.lastname@example.org.
AbstractPIK3CA 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.
VersionFinal published version
SponsorsNational Institutes of Health [F30CA180235, R01DE024728, R01CA098372, R01DE023685, P50CA097190, P30CA047904]; American Head and Neck Society; V Foundation for Cancer Research; American Cancer Society; Department of Veterans' Affairs Career Development Award Biomedical Laboratory Research Development
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