Abstract

Point-of-Care EFIRM-based Liquid Biopsy for Actionable EGFR Mutations in NSCLC

David Wong, Director, University of California Los Angeles

Constitutive activation of epithelial growth factor receptor (EGFR) is prevalent in epithelial cancers, particularly in non-small-cell lung carcinoma (NSCLC). EGFR mutation predicts sensitivity to EGFR-targeted therapy and mutation detection is mainly based on tissue biopsy, which is invasive, expensive and time-consuming. Non-invasive, real-time, point-of-care, inexpensive detection and monitoring of EGFR mutations in NSCLC patients is highly desirable. We developed a novel core technology, Electric Field-Induced Release and Measurement (EFIRM), relying on a multiplexible electrochemical sensor that can detect EGFR mutations directly from body fluids. EFIRM Liquid Biopsy (eLB) for EGFR mutation detection was established in vitro, and correlated with tumor size from xenografted mice. In two independent blinded clinical studies of 44 and 67 NSCLC patients, our studies indicated that eLB can detect actionable TKI-responsive mutations (L858R and exon 19del) in plasma and saliva with near perfect concordance with tissue/biopsy genotyping (AUC >0.94). Our data indicate that EFIRM is effective, accurate, rapid, user-friendly, and cost effective for the detection of EGFR mutations in plasma and saliva of NSCLC patients.