Project Description Narrative:
Pancreatic cancer is an extremely lethal form of cancer. More than 90% of pancreatic cancers are pancreatic ductal adenocarcinomas (PDACs). PDAC is ranked seventh in cancer-causing deaths in the world and ranked third in the United States. Despite enormous efforts in trying to improve diagnosis and treatment, the prognosis of PDAC is poor, with the five-year survival rate being less than 10%. According to the North American Association of Central Cancer Registries, approximately 64,050 patients are expected to be diagnosed with pancreatic cancer, and approximately 50,550 patients are expected to die in 2023 from this cancer in the U.S.; hence, it is the second leading cancer-related cause of death after lung cancer.
The mortality rate of pancreatic cancer is slightly greater in Wisconsin than in the U.S., but the mortality rate in Wisconsin is disproportionately higher in Black versus White people (17.4 versus 12.8 per 100,000 people, respectively). Apart from hereditary underlying genetic mutations, the risk factors associated with development of PDAC include alcohol consumption, cigarette smoking, obesity and/or diet, diabetes mellitus, and chronic pancreatitis. The poor prognosis of PDAC is mainly due to lack of effective, early diagnostic methods and lack of efficient treatment, highlighting the necessity for better understanding of the basic biology and identification of novel therapeutic targets of this disease.
This project aims to characterize the ATP5E gene, which encodes the mitochondrial ATP synthase epsilon subunit, and determine whether it plays a role in the early progression of mouse and human PDAC. The long-term objective of this study is to understand the mechanism(s) of how ATP5E in cancer-associated fibroblasts (CAFs) communicates with tumor epithelial cells expressing mutant RAS to elicit the early stages of tumor initiation, hyperplasia.