Mitochondrial uncoupling protein 2 and pancreatic cancer: a new potential target therapy

Overall 5-years survival of pancreatic cancer patientsis nearly 5%, making this cancer type one of the mostlethal neoplasia. Furthermore, the incidence rate ofpancreatic cancer has a growing trend that determinesa constant increase in the number of deceases causedby this pathology. The poor prognosis of pancreaticcancer is mainly caused by delayed diagnosis, earlymetastasis of tumor, and resistance to almost all testedcytotoxic drugs. In this respect, the identification ofnovel potential targets for new and efficient therapiesshould be strongly encouraged in order to improvethe clinical management of pancreatic cancer. Somestudies have shown that the mitochondrial uncouplingprotein 2 (UCP2) is over-expressed in pancreatic canceras compared to adjacent normal tissues. In addition,recent discoveries established a key role of UCP2 inprotecting cancer cells from an excessive productionof mitochondrial superoxide ions and in the promotionof cancer cell metabolic reprogramming, includingaerobic glycolysis stimulation, promotion of cancerprogression. These observations together with thedemonstration that UCP2 repression can synergize withstandard chemotherapy to inhibit pancreatic cancercell growth provide the molecular rationale to considerUCP2 as a potential therapeutic target for pancreaticcancer. In this editorial, recent advances describingthe relationship between cancer development andmitochondrial UCP2 activity are critically provided.