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

Abstract

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.

Learning Objectives

  1. To gain an understanding of the mutational landscape of head and neck squamous cell carcinoma
  2. To explore patient derived xenografts (PDXs) as cancer models and appreciate the utility of PDX clinical trials
  3. To learn about genomic predictors of response to PI3Ka-inhibition

Download Poster (PDF)

No presentation materials have been uploaded for this presentation. Please check back again later.

Scheduling Details

Posters can be seen in the Gray/Palmer/Pope Ballroom. This room will be open on Sunday, June 12 from 09:00 to 17:00, and on Monday, June 13 from 09:00 to 16:00.

Authors' Contact Details

Corresponding Author: Dr. Anthony Nichols

Senior Author: Dr. Anthony Nichols

The corresponding author of this presentation has not yet consented to having their email address published online.