Published online Mar 21, 2015. doi: 10.3748/wjg.v21.i11.3232
Peer-review started: October 14, 2014
First decision: December 11, 2014
Revised: December 18, 2014
Accepted: February 5, 2015
Article in press: February 5, 2015
Published online: March 21, 2015
Overall 5-years survival of pancreatic cancer patients is nearly 5%, making this cancer type one of the most lethal neoplasia. Furthermore, the incidence rate of pancreatic cancer has a growing trend that determines a constant increase in the number of deceases caused by this pathology. The poor prognosis of pancreatic cancer is mainly caused by delayed diagnosis, early metastasis of tumor, and resistance to almost all tested cytotoxic drugs. In this respect, the identification of novel potential targets for new and efficient therapies should be strongly encouraged in order to improve the clinical management of pancreatic cancer. Some studies have shown that the mitochondrial uncoupling protein 2 (UCP2) is over-expressed in pancreatic cancer as compared to adjacent normal tissues. In addition, recent discoveries established a key role of UCP2 in protecting cancer cells from an excessive production of mitochondrial superoxide ions and in the promotion of cancer cell metabolic reprogramming, including aerobic glycolysis stimulation, promotion of cancer progression. These observations together with the demonstration that UCP2 repression can synergize with standard chemotherapy to inhibit pancreatic cancer cell growth provide the molecular rationale to consider UCP2 as a potential therapeutic target for pancreatic cancer. In this editorial, recent advances describing the relationship between cancer development and mitochondrial UCP2 activity are critically provided.
Core tip: The dramatic poor prognosis of pancreatic cancer forces towards the identification of novel efficient therapeutic targets against this neoplasia. Overexpression of uncoupling protein 2 (UCP2) and its functional involvement in cancer development, reactive oxygen species production, and cancer metabolic reprogramming may represent the rationale and the starting point for future drug design projects focused on the identification of specific UCP2 inhibitors as innovative therapeutic tool against pancreatic cancer.