UC San Diego

Pancreatic ductal adenocarcinoma (PDAC) is the 3rd leading cause of cancer-related death in the United States. PDAC is highly metastatic with the liver being the most common site of metastasis. Notably, even after surgical resection of early stage of PDAC tumors, recurrence often occurs in the liver instead of the primary site that was surgically treated, suggesting the existence of micrometastasis in the liver of early-stage diseases. There is currently no approach to treat or prevent liver metastasis besides chemotherapy that is highly toxic and lacks efficacy. Therefore, new therapeutic targets need to be investigated to make a difference in patients’ outcomes. My thesis research project is to investigate small ubiquitin-like modification (SUMOylation) as a target to prevent and treat PDAC liver metastasis. SUMOylation is a reversible post-translational modification involving the attachment of a SUMO protein covalently to a target protein. Previous studies have shown that SUMOylation is required for KRas and c-Myc-dependent oncogenesis that are main drivers of PDAC progression. In addition, SUMOylation has been established as a target for activation of anti-tumor immunity. My findings suggest that SUMOylation inhibition can block PDAC liver metastasis. The mechanisms could be through both immune-mediated and tumor-specific effects.