Molecular and cellular characterization of the hepatic pre-metastatic niche in pancreatic cancer, and the role of extracellular vesicles as biomarkers of metastasis

Pancreatic cancer (PaCa) is a highly lethal malignancy with rising incidence and limited treatment options. Liver metastasis represents the most aggressive outcome of PaCa and is nearly always fatal.

Improved understanding of the early steps of metastasis can lead to development of diagnostic biomarkers to stratify patients according to their metastatic risk, and identify novel therapeutic vulnerabilities for interruption of the metastatic cascade.

Based on my preliminary data, I hypothesize that the liver has an active role in the progression of this nefarious disease, through reciprocal communication with the primary tumor by means of secreted factors, such as extracellular vesicles (EVs), as well as modulation of anti-tumor immune response.

In this project, I will assess the biomarker and therapeutic target potential of EVs and the pre-metastatic liver in PaCa patients.

I will use proteomics to characterize PaCa EVs, and define the pre-metastatic liver by focusing on phenotypic and functional characterization of hepatic immune cells. I will then correlate these data with patterns of recurrence.

I also hope to identify novel therapeutic targets that may be advanced to next phase clinical trials in the next 5-years.

By exploring novel sources of biomarkers and targets for therapies, such as liver biopsies and EV-based liquid biopsies, I anticipate to define signatures that capture the pre-metastatic “window of opportunity”, providing new ways to improve PaCa survival.