Biological and therapeutic significance of tissue transglutaminase in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDA) is one of the deadliest cancers world-wide with an estimated annual incidence and mortality rates of approximately 6,500 cases in the UK, over 40,000 cases in Europe, 19,000 cases in Japan and over 30,000 cases in the United States. Difficulty to diagnose the disease at an early stage, rapid progression and intrinsic resistance to currently available therapies are major factors that contribute to poor disease outcome in these patients (overall 5 years survival, < 3%). Identification of cancer cell-encoded genes that contribute to the development of intrinsic resistance and metastatic spread of the PDA tumors, may yield immediate clinical benefits in terms of revealing new therapeutic targets for effective treatment of the disease. This article discusses the significance of tissue-type transglutaminase (TG2) whose expression is elevated in the majority of PDA tumors and cell lines. Based on the published data and the results discussed in this review, TG2 appears to be a promising target for containment and treatment of this formidable disease.