Functional validation of dibenzyl diselenide as antineoplastic agent

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in the worldwide. It is currently the seventh leading cause of cancer death in the world and it is estimated to become the highest contributor to cancer related death by 2030. The 5-year survival rate spaces from 2% to 9%. Different statistical reports show that there is a continuous increase both in the number of cases and in deaths. What makes this cancer so deadly is the difficulty in diagnosis at an early stage, in which one it could be still possible to intervene, and the difficulty of the various kind of therapies to access the tumor site, which creates a special type of microenvironment called TME (tumor microenvironment) which limits the access to drugs and immune system cells. In this context, the understanding of the molecular mechanisms underling PDAC onset and progression is crucial. Particular attention should also be paid to the search for new therapeutic strategies that can elude the strong resistance to drugs by this aggressive tumor. In this thesis project, I evaluated the antineoplastic activity of “dibenzyl diselenide ”(DBDS), a diselenide belonging to the family of the organoselenium compounds. To this goal, I employed both murine and human cancer cell lines, and tested growth inhibition (including IC50) and cell death pathways in vitro. I also demonstrated efficient anti-tumor activity in murine mouse models. My work shows that DBDS induces non-apoptotic cell death and inhibits pancreatic cancer growth, alone or in combination with other compounds already in use in therapy.