Although pathways such as the ASK1-p38-MAPK pathway have been implicated in NNMT-mediated resistance of colorectal cancer cells to 5-FU [125], given the strong cytoprotective effects of Akt signalling, along with the well-documented regulation of Akt phosphorylation demonstrated by us and others in a wide variety of cancers, it is likely that the NNMT–Akt axis is heavily involved in acquired drug resistance. The gene discussed is MAP3K5; the disease is colorectal cancer.