Collectively, these results suggest that for AR negative AKR1C2 positive (AR−/AKR1C2+) ESCC, AKR1C2 mediates activation of PI3K/AKT pathway may be an alternative to DHT‐AR pathway, which uses androgen metabolites to activate a classic tumour signalling pathway. Here, AKR1C2 is linked to esophageal squamous cell carcinoma.