Other layers are epigenetic and metabolic rewiring: in colorectal cancer (CRC), proteasome inhibition of DNA methytransferase (DNMT)1/3B synthesis by protein kinase B (AKT)/mammalian target of rapamycin (mTOR) blockade that remodeled DNA methylation and transcriptomic programs to connect proteasome activity with epigenetic plasticity (73); conversely, inhibition of glutamate-to-glutathione flux in CRC activated reactive oxygen species (ROS) pathways and promoted immunoproteasome activity, enhancing antigenicity and T-cell recognition (74). Here, AKT1 is linked to colorectal cancer.