PIK3CA mutation has been recommended as a sensitive biomarker for alpelisib for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer due to the promising results from a SOLAR-1 phase III trial (NCT02437318).13 As PIK3CA mutation is much less frequent in ESCC than that in breast cancer, it would be worthwhile to discover additional biomarkers capable of predicting the efficacy of PI3Kα inhibitors on a genome-wide scale. Here, PIK3CA is linked to esophageal squamous cell carcinoma.