Descrizione del progetto
La scoperta di un nuovo meccanismo che provoca la malattia nell’oncogenesi pancreatica
I meccanismi molecolari che portano all’insorgenza del cancro pancreatico sono tuttora sfuggenti e al giorno d’oggi quasi non esiste alcuna terapia mirata per combatterlo. L’ipotesi su cui lavora il progetto pHioniC, finanziato dall’UE, è che il pancreas sia un ambiente acido unico potenzialmente in grado di agevolare l’innesco e la progressione del cancro pancreatico. Il succo pancreatico alcalino secreto per neutralizzare il chimo acido in arrivo dallo stomaco determina cambiamenti temporali nei livelli di pH che possono comportare mutazioni oncogeniche. I ricercatori mapperanno il pH dell’ambiente pancreatico e approfondiranno il meccanismo attraverso cui può influenzare la progressione della malattia. Inoltre, esploreranno i potenziali interventi sul pH per alterare il decorso patologico.
Obiettivo
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.
Campo scientifico
Not validated
Not validated
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
MSCA-ITN - Marie Skłodowska-Curie Innovative Training Networks (ITN)Coordinatore
48149 MUENSTER
Germania