Accordingly, these results suggested that silencing of SOX17 in ESCC may play an important role in the development of NRF2-addiction in the resistant cells, and these resistant cells rely more on the dysregulation of SOX17/NRF2 axis to maintain their resistance, making it a promising therapeutic target for overcoming resistance. The gene discussed is NFE2L2; the disease is esophageal squamous cell carcinoma.