The role of STAT3 on pancreatic tumor radiosensitization


Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal tumor, with a 5-year survival rate of approximately 11%. While RT is used to mitigate tumor recurrence in advanced pancreatic cancer, it frequently leads to severe gastrointestinal side effects. An innovative strategy to confront these challenges involves altering the tumor microenvironment to enhance its responsiveness to RT.
Our prior research has unveiled a significant upregulation of STAT3 in mouse orthotopic pancreatic tumors post-RT, as compared to untreated tumors. Preliminary data suggest that genetic deletion of STAT3 inhibits the tumor growth of pancreatic tumors. Additionally, STAT3 has been implicated as a central integrator of multiple profibrotic and chronic inflammatory signals. However, the significance of host STAT3 induction post-RT within the PDAC tumor microenvironment is still poorly understood. Our studies seek to elucidate the mechanisms by which host STAT3 contributes to the development of radioresistance, with the ultimate aim of translating these insights into clinical trials for PDAC patients undergoing RT.