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Ref Type Journal Article
PMID (30683736)
Authors 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, Grandis JR
Title Use of nonsteroidal anti-inflammatory drugs predicts improved patient survival for PIK3CA-altered head and neck cancer.
Journal The Journal of experimental medicine
Vol 216
Issue 2
Date 2019 02 04
URL
Abstract Text 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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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
PIK3CA F744L missense unknown PIK3CA F744L does not lie within any known functional domains of the Pik3ca protein (UniProt.org). F744L has been identified in the scientific literature (PMID: 30683736), but has not been biochemically characterized and therefore, its effect on Pik3ca protein function is unknown (PubMed, Apr 2020).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
PIK3CA R38C head and neck squamous cell carcinoma sensitive Sulindac Preclinical - Pdx Actionable In a preclinical study, Clinoril (sulindac) treatment reduced tumor growth rate in patient-derived xenograft (PDX) models of head and neck squamous cell carcinoma harboring PIK3CA mutations, including PIK3CA R38C (PMID: 30683736). 30683736
PIK3CA M1043V head and neck squamous cell carcinoma sensitive Sulindac Preclinical - Pdx Actionable In a preclinical study, Clinoril (sulindac) treatment reduced tumor growth rate in patient-derived xenograft (PDX) models of head and neck squamous cell carcinoma harboring PIK3CA mutations, including PIK3CA M1043V (PMID: 30683736). 30683736
PIK3CA H1047R head and neck squamous cell carcinoma predicted - sensitive Sulindac Preclinical - Cell culture Actionable In a preclinical study, head and neck squamous cell carcinoma cell lines harboring PIK3CA H1047R demonstrated increased sensitivity to Clinoril (sulindac) compared to cell lines with wild-type PIK3CA, resulting in decreased proliferation in culture (PMID: 30683736). 30683736
PIK3CA M1043V head and neck squamous cell carcinoma sensitive Celecoxib Preclinical - Pdx Actionable In a preclinical study, Celebra (celecoxib) treatment reduced tumor growth rate in a patient-derived xenograft (PDX) model of head and neck squamous cell carcinoma harboring PIK3CA M1043V (PMID: 30683736). 30683736
PIK3CA mutant lung non-small cell carcinoma predicted - sensitive Sulindac Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines harboring either a PIK3CA mutation or PIK3CA amplification demonstrated increased sensitivity to Clinoril (sulindac) compared to cell lines with wild-type PIK3CA, resulting in decreased proliferation in culture (PMID: 30683736). 30683736
PIK3CA E542K PIK3CA F744L head and neck squamous cell carcinoma sensitive Sulindac Preclinical - Pdx Actionable In a preclinical study, Clinoril (sulindac) treatment reduced tumor growth rate in patient-derived xenograft (PDX) models of head and neck squamous cell carcinoma harboring PIK3CA mutations, including a model harboring PIK3CA E542K and PIK3CA F744L (PMID: 30683736). 30683736
PIK3CA amp lung non-small cell carcinoma predicted - sensitive Sulindac Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung cancer cell lines harboring either a PIK3CA mutation or PIK3CA amplification demonstrated increased sensitivity to Clinoril (sulindac) compared to cell lines with wild-type PIK3CA, resulting in decreased proliferation in culture (PMID: 30683736). 30683736