Although several NOTCH inhibitors have been developed, such as γ-secretase and transcriptional complex inhibitors, they broadly target NOTCH1-4 signaling, often causing gastrointestinal toxicity due to nonspecific disruption, thereby limiting potential utility in the clinic.39–41 As a consequence, thus far, no FDA approval has been given for NOTCH inhibitors for CRC treatment. The gene discussed is NOTCH1; the disease is colorectal carcinoma.