2018 CSO General Scientific Program
“A controlled trial of HNSCC patient-derived xenografts reveals broad efficacy of PI3K-alpha inhibition in controlling tumor growth”
Kara M. Ruicci, John Yoo, Kevin Fung, Danielle MacNeil, John W. Barrett, Paul C. Boutros, Laurie Ailles, Anthony C. Nichols
Introduction: Head neck squamous cell carcinomas (HNSCCs) frequently contain PIK3CA mutations, thus there is increasing interest in PI3Ka-inhibition for HNSCC treatment. Identification of predictive biomarkers would advance the application of PI3Ka-targeted drugs for patients to achieve maximal benefit. Objectives: To date, biomarker studies have largely focused on cell lines, which has rarely enabled accurate predictions of drug efficacy. Recently, patient derived xenograft (PDX) clinical trials have been introduced as a platform to interrogate interpatient response heterogeneity. PDX clinical trials have shown close correlations closely with patient outcomes. Methods: Using a PDX clinical trial of 80 genomically-characterized xenografts derived from 20 HNSCC tumors, we examined PI3K-inhibitor response. Results: We found EGFR, AKT1 and CSMD1 copy number aberrations, but not PIK3CA mutations, to be associated with responsiveness to PI3Ka-inhibition. Conclusions: Further, we found PI3Ka-inhibition to be almost globally tumoristatic in xenografts, emphasizing its potential as a stabilizing neoadjuvant therapy for HNSCC patients.
- To gain an understanding of the mutational landscape of head and neck squamous cell carcinoma
- To explore patient derived xenografts (PDXs) as cancer models and appreciate the utility of PDX clinical trials
- To learn about genomic predictors of response to PI3Ka-inhibition
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Corresponding Author: Dr. Anthony Nichols
Senior Author: Dr. Anthony Nichols
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