Project description
Discovery of a novel disease-causing mechanism for pancreatic oncogenesis
The molecular mechanisms that give rise to pancreatic cancer remain elusive with hardly any targeted therapies available today. The working hypothesis of the EU-funded pHioniC project is that the pancreas has a unique acidic environment that may facilitate pancreatic cancer initiation and progression. The alkaline pancreatic juice secreted to neutralise the acidic chyme that arrives from the stomach induces temporal changes in pH levels which may drive oncogenic mutations. Researchers will map the pancreatic pH landscape and investigate the mechanism by which it can influence disease progression. Moreover, they will explore potential pH interventions to alter the disease course.
Objective
pHioniC brings together highly synergistic expertise, research and training facilities to investigate pancreatic ductal adenocarcinoma (PDAC), a frequent and aggressive cancer that is still incurable. The programme’s central hypothesis has a strong grounding in the physiology of the exocrine pancreas. Secretion of the alkaline pancreatic juice, normally associated with digestion, leads to acidifications of the pancreas stroma resulting in an acid adaptation of pancreatic cells. We are first to propose that this adaptation facilitates PDAC initiation and progression by selecting for more aggressive phenotypes in interplay with PDAC driver mutations. pHioniC will:
(i) develop models (e.g. pancreas-/PDAC-specific pH-indicator mouse) to map the pH landscape in the normal and diseased pancreas,
(ii) characterize the impact of the acidic microenvironment in PDAC development and
(iii) design bespoke approaches to the treatment of PDAC that exploit the unique physiology of the pancreas and utilize a combination of nanocarrier and antibody technology for targeting.
Thereby, pHioniC provides an innovative interdisciplinary and intersectoral training for ESRs at the forefront of oncological research.
pHioniC comprises excellent complementary basic-research, clinical, and in silico laboratories that provided the seed discoveries for this novel concept, and industrial partners with a track record in therapeutic and diagnostic development in oncology. This highly synergistic team combines the state-of-the-art research tools and translational opportunities needed to meet the most ambitious doctoral programmes. pHioniC training for ESRs covers the fields of ion transport, oncology, imaging, bioinformatics and antibody technology, and is complemented by extensive transferable skills and personalised training elements. pHioniC will establish a lasting contribution towards European doctoral training beyond the lifetime of the project.
Fields of science
Keywords
Programme(s)
Coordinator
48149 MUENSTER
Germany