Contacts:
Supervisor(s):
Ilaria Bonaduce
Title of the PhD project:
Precision proteomics of pancreatic adenocarcinoma
Abstract of the PhD project:
Pancreatic cancer is a major unsolved health problem with less than 10% of patients alive 5 years after diagnosis. Approximately 80% of patients are diagnosed after the tumor has spread, and so there is an urgent need for earlier diagnosis. Pancreatic cancer is the archetypal hypoxic tumor. Hypoxia is a non-physiological level of oxygen and leads to increased mobility and metastasis, alters tumor cell metabolism, and contributes to therapy resistance by inducing cell quiescence and drug efflux. Within the hypoxic environment autophagy is central to PDAC metabolism (glutamine metabolism through macropinocytosis-associated autophagy and alanine secretion by stromal cells (pancreatic stellate cells, PSCs) that is dependent on PSC autophagy). There is shared molecular machinery between exosome biogenesis and autophagy, and recent studies have revealed substantial crosstalk between these two processes. Accordingly, the altered autophagy in the highly hypoxic regions of PDAC are expected to be mirrored by altered exosomal molecular signatures, and importantly exosomal surface markers that would enable the isolation of PDAC-specific exosomes. We hypothesize that cell-and-phenotype-specific exosome analysis would allow the identification of PDAC specific biomarkers that could enable earlier detection.
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