Depending on the CRC settings, a dichotomy for the role of NOTCH1 pathway activation is reported: while in sporadic or hereditary models of CRC NOTCH1 acts as an oncogene and is required for adenoma formation19 and cancer progression20, in colitis-associated cancer (CAC) NOTCH1 seems to have a tumor suppressor role and its inhibition is associated with decreased apoptosis21. The gene discussed is NOTCH1; the disease is neoplasm.