As the first PI3Kα-selective inhibitor approved by the Food and Drug Administration, alpelisib is currently tested in ESCC patients in clinical trials.11 Due to the high heterogeneity in the genetic alterations in ESCC, the response of ESCC to BKM120, a pan-PI3K inhibitor, was highly variable.12 It is of great importance to identify potential biomarkers to predict or monitor the efficacy of PI3Kα inhibitors in an aim to improve the clinical responsive rate in ESCC. The gene discussed is PIK3CA; the disease is esophageal squamous cell carcinoma.