The Dutch Cancer Society (KWF Kankerbestrijding) has awarded a total of 5.5 million euro to ten Amsterdam UMC research groups for cancer research. One of the project proposals selected is entitled “Central role of exosomes in liver colonization and for selection of effective drugs against metastatic pancreatic cancer” (€ 599.052) by principal investigator Dr. Elisa Giovannetti and collaborators Prof. G. Kazemier, Dr. M. Pegtel and Dr. R. Baglio. This team aims to elucidate the role of extracellular vesicles in mediating the crosstalk between metastatic pancreatic cancer cells and the tumor microenvironment, in order to interfere with this process for the development of new therapeutic and clinical management strategies.
Metastasis is the primary contributor to the dismal outcome of pancreatic cancer and most patients die of hepatic failure from their liver being taken over by tumor. The liver is known as the primary metastatic target organ in pancreatic cancer, and patients with liver metastasis have worse 5-year survival rates compared to patients with lung and nodal metastasis.
However, despite the morphological closeness of these organs and the common infiltration of the vasculature, the extremely high frequency of liver metastasis in pancreatic cancer is still not yet fully understood. Recent studies suggest an important role of molecular and cellular interactions between the primary and metastatic tumors and their surrounding tissues. Remarkably, in some mouse models extracellular vesicles (EVs) seem critical for the development of liver metastatic niches, although the molecular mechanisms underlying this effect are largely unknown. The present study will evaluate in innovative preclinical models and tissue samples the specific role of EVs in pancreatic cancer liver metastasis expansion and reseeding.
This research has major clinical implications since pharmacological inhibition of metastatic progression can enhance the efficacy of current treatments, slow down or prevent disease progression, and increase survival and quality-of-life of pancreatic cancer patients. The ultimate goal is indeed to improve pharmacological treatment and personalized clinical management of patients with metastatic pancreatic cancer.
