A controlled trial of HNSCC patient ‐derived xenografts reveals broad efficacy of PI3Kα inhibition in controlling tumor growth

Head and neck squamous cell carcinomas (HNSCCs) frequently harbor alterations in the PI3K/AKT/mTOR signalling axis, particularly in thePIK3CA gene. PI3K ‐targeted agents have therefore gained considerable preclinical and clinical interest as emerging therapies for HNSCC. Identification of predictive biomarkers of response would advance the clinical application of PI3K‐targeted drugs for patients in order to achieve maximal benefit. To date, stud ies of drug biomarkers have largely focused on screening cell lines, with much more limitedin vivo testing, usually only as validation. This approach has rarely enabled accurate predictions of clinical efficacy. Recently, clinical trials of PDX models (PDX clinical trials) have been introduced as a preclinical approach to interrogate interpatient response heterogeneity. Already, PDX clinical trial responses have been demonstrated to correlate closely with patient outcomes. Here, using both an HNSCC specific, 28 ‐cell line panel and a PDX clinical trial of 80 xenografts derived from 20 unique HNSCC tumors, we systematically examine patterns of response to PI3K inhibition in HNSCC. We findEGFR,AKT1 andCSMD1 copy number aberrations, but notPIK3CA mutations, to be associated with responsiveness to PI3K ‐targeted drugs. Further, we reveal PI3Kα inhibition to be almost globally tumoristatic in HNSCC xenografts regardless ofPIK3CA mutational status, emphasizing its potential as a stabilizing neoadjuvant therapy for HNSCC patients.
Source: International Journal of Cancer - Category: Cancer & Oncology Authors: Tags: Short Report Source Type: research