High SIRT5expression in CRC patients expressing wild-type KRAS is also associatedwith increased tumor recurrence and poor survival.144 In this context, it was shown that drug resistance wasgained by the activation of the ROS scavenger protein thioredoxinreductase 2 (TrxR2).144 Mechanistically,the SIRT5-mediated desuccinylation of succinate dehydrogenase complexsubunit A (SDHA) and the inhibition of its enzymatic activity leadto higher levels of succinate, which determines TrxR2 activation (Figure 4). The gene discussed is SIRT5; the disease is neoplasm.