Pancreatic ductal adenocarcinoma (PDAC) is the fourth most common cause of cancer-related death with 5-year survival rate not exceeding 7%. The cancer from pancreatic ducts arises from the accumulation of genetic mutations that allow epithelial cells to proliferate outside normal checks and controls, and eventually invade remote organs. As a unique feature of this ductal epithelium, the basolateral side features a chemical milieu that is acidic, especially during the secretory phase when large fluxes of bicarbonate (a base) are transferred to the luminal (opposite) pole. Low pH is postulated to be a driving force behind tumorigenesis, although a by-stander effect cannot be excluded. In order to test whether pH can meaningfully influence cancer behaviour, I perform high-throughput phenotypic screens that assemble a quantitative description of acid-sensing and acid-handling in a panel of cell lines, which will allow to define the pH phenotype from a functional viewpoint, and produce a mathematical description which could then feed into in silico models of somatic evolution to explore processes that are not readily attainable experimentally.
This DPhil project is funded by European Commission, Marie Sklodowska Curie Innovative Training Network and is a part of pH and Ion Transport in Pancreatic Cancer – pHioniC – consortium which includes 12 European institutions with a common goal to further describe, characterize and utilize in the clinical approach the link between pH and carcinogenesis in the pancreas.