Genomic Profiling of HER2‐Positive Gastric Cancer: PI3K/Akt/mTOR Pathway as Predictor of Outcomes in HER2‐Positive Advanced Gastric Cancer Treated with Trastuzumab

摘要

Background.HER2‐positive gastric cancer (GC) affects 7%–34% of patients with GC. Trastuzumab‐based first‐line treatment has become the standard of care for HER2‐positive advanced gastric cancer (AGC). However, there are no clinically validated biomarkers for resistance to HER2‐targeted therapies. Upregulation of PI3K pathway and tyrosine kinase receptor (TKR) alterations have been noted as molecular mechanisms of resistance in breast cancer. Our study aimed to perform a molecular characterization of HER2‐positive AGC and investigate the role of PI3K/Akt/mTOR signaling pathway activation and TKR gene copy number (GCN) gains as predictive biomarkers in HER2‐positive AGC treated with trastuzumab.