NMNAT1 and neoplasm: Another possible reason for the clinical failure of epacadostat is that the blockade of the Kyn pathway regulates metabolic adaptation in the tumor microenvironment and triggers the activation of alternative NAD generation pathways driven by multiple mechanisms, including increasing the mRNA expression of various enzymes in the NAD synthesis pathway, such as NAPRT, NADSYN, NMNAT, SLC7A5.