Finally, we provide evidence about the synergistic effects induced by GSIs with OXP or 5FU chemotherapeutic agents, in sustaining Jag-ICD-dependent multidrug resistance, unveiling a novel mechanism of drug resistance in Jagged1 CRC cells, where Jag1-ICD may function as a nuclear effector with the ability to sustain the pro-proliferative and anti-apoptotic events (Figure 4D). This evidence concerns the gene JAG1 and colorectal carcinoma.