TP53 and cancer: In conclusion, even though further investigations are required to better understand the repercussion of the reprogramming of the HBP and O-GlcNAcylation processes in the establishment of the senescent phenotype, our results strongly support that combining O-GlcNAcylation inhibition to conventional chemotherapies, to induce a senescence-apoptosis shift of cancer cells, could offer a promising strategy for MSI/dMMR/p53 unmutated CRC treatment potentially averting senescence escape and relapse.