PIK3CA and esophageal squamous cell carcinoma: CYH33 is a novel PI3Kα-selective inhibitor with a distinctive chemical structure, which was discovered in our previous work and is in phase I-II clinical trials for the therapy of advanced solid tumors including ESCC (NCT05043922, NCT04586335 and NCT03544905).14,15 CYH33 demonstrated a manageable safety profile, linear pharmacokinetics, and encouraging preliminary anti-tumor activity.15–17 Preliminary results indicated that PIK3CA-mutated ESCC patients are responsive to CYH33 treatment.