Scientists reprogrammed human pancreatic cancer cells to quiescent acinar like cells
Pancreatic ductal adenocarcinoma (PDA) is a fatal malignancy and one of the most difficult human cancers to treat. Medical science has made great strides in the early diagnosis and treatment of many other type of cancers such as breast cancer, prostate cancer, and lung cancer. However, the prognosis of pancreatic cancer remains an elusive clinical challenge largely because of the difficulty of making an early diagnosis. Patients with pancreatic cancer typically develop very few symptoms in the early stage, which could easily mislead physicians. The lethal nature of this cancer makes it the fourth leading cause of cancer death in the United States, with a median survival of less than 6 months and a dismal 5-years survival rate of 3%–5%. So far, no curative treatments are available to treat advanced stages of this disease. Surgery offers only a minimal chance to cure pancreatic cancer; however, less than 20% of patients diagnosed with pancreatic cancer are considered for surgical resection. Chemoradiotherapy and radiation have shown some success in reducing tumor growth and prolonging patients' life spans, but the beneficial effects of these treatments are limited in long run.
Recently, a breakthrough was made by scientists at the University of California, San Diego, Purdue University, and Sanford-Burnham Medical Research Institute (SBMRI) in La Jolla, which may pave the way for future pancreatic cancer treatment . The team showed that PDA cells with tumorigenic properties can be forced back towards an acinar-like differentiated state with greatly reduced tumorigenic properties. The forced expression of transcription factor E47 successfully inhibited tumorigenesis in human PDA cells in vitro. Transcription factor E47 typically controls genes involved in growth and differentiation. For the first time, researchers have shown that over-expression of a single gene can reduce the tumor-promoting potential of pancreatic adenocarcinoma cells and reprogram them toward their original cell type. Furthermore, transplantation of reprogrammed cancer cells into mice led to drastically diminished tumors. The investigation has opened the door to a new treatment for pancreatic ductal adenocarcinoma, coaxing cancer cells to back to a non-threatening phenotype.
The study provides an important transformative development in the field of pancreatic cancer research, and this approach could be applied to other types of cancers too. Although the preliminary results demonstrate a remarkable outcome further work will need to be done to understand the molecular underpinnings of this disease.
 Kim et al., The Basic Helix-Loop-Helix Transcription Factor E47 Reprograms Human Pancreatic Cancer Cells to a Quiescent Acinar State With Reduced Tumorigenic Potential. Pancreas 2015.