Indeed, the upregulation of the Notch1/HES1 axis and Jagged1 was associated with acquired resistance to 5-FU in colon cancer cells; co-treatment of colon cancer cells with GSI34 in CRC cells was synergistic with 5-FU [187,425,426,547]; and the knockdown of JAG1 and JAG2 sensitized colon cancer cells to 5-FU and enhanced the induction of apoptosis [427]. Here, HES1 is linked to colorectal carcinoma.