Edna Cukierman

Abstract Pancreatic ductal adenocarcinoma remains one of the deadliest malignancies, characterized by late diagnosis, aggressive biology and limited therapeutic success. Advances in multiagent chemotherapy have improved outcomes across disease stages, whereas precision medicine approaches are reshaping treatment paradigms. Personalized RNA vaccines and oncogenic KRAS-directed agents represent emerging immunological and molecular frontiers.

Abstract Levels of pancreatic ductal adenocarcinoma (PDAC) are increasing, with epidemiological studies nominating obesity, altered cholesterol metabolism, and elevated lipids as risk factors. In prior studies, we determined that elevated expression of sterol regulatory element binding protein 2 (SREBP2), a transcription factor directing lipid biosynthesis, promoted epithelial-mesenchymal transition and aggressive tumorigenesis in the KPC (LSL-KrasG12D;Trp53f/f;Pdx1-Cre) mouse model of PDAC.

Abstract This phase I, dose-escalation trial evaluates the safety of combining interferon-gamma (IFN-γ) and nivolumab in patients with metastatic solid tumors. Twenty-six patients are treated in four cohorts assessing increasing doses of IFN-γ with nivolumab to evaluate the primary endpoint of safety and determine the recommended phase two dose (RP2D). Most common adverse events are low grade and associated with IFN-γ. Three dose limiting toxicities are reported at the highest dose cohorts.