NOTCH1 and esophageal squamous cell carcinoma: Three molecular subtypes of esophageal squamous cell carcinoma (ESCC) have been described: ESCC1, with mutations of NRF2, associated with a poor prognosis and resistance to chemo-radiotherapy; ESCC2, in which NOTCH1 or ZNF750 are frequently mutated; and ESCC3, characterized by alterations that activate the PI3K pathway.