The phosphatidylinositol 3-kinase (PI3K) integrates signals from diversified environmental cues and regulates various cellular processes including metabolism, proliferation, apoptosis and cytoskeletal rearrangement.8 Large scale next-generation sequencing has evidenced that the PI3K pathway is often hyper-activated in ESCC.9 Mutation or amplification of PIK3CA encoding the catalytic subunit p110α has been found in 13% or 30% of ESCC patients respectively.10 Moreover, hyper-activation of receptor tyrosine kinases (RTKs) or functional loss of PTEN also results in active PI3K signaling. The gene discussed is PTEN; the disease is esophageal squamous cell carcinoma.