Finally, we provide evidence about synergistic effects induced by GSIs with OXP or 5FU chemotherapeutic agents, in sustaining Jag1-ICD-dependent multidrug resistance, unveiling a novel mechanism of intrinsic chemoresistance in Jagged1 CRC cells, where Jag1-ICD may function as a nuclear effector. This evidence concerns the gene JAG1 and colorectal carcinoma.