Some studies have identified functional molecules with mutant p53.72–76 Although our present study revealed that inhibiting ACLY and ALDOA activities effectively blocks the malignancy of TP53-mutant ESCC cells, further functional assays and mechanistic investigations are needed to determine whether these two metabolic enzymes can serve as synthetic lethal targets for treating TP53-mutated ESCC cells. Here, TP53 is linked to esophageal squamous cell carcinoma.