Topic: Overcoming Mechanisms of Therapeutic Resistance in Pancreatic Cancer

Pancreatic cancer, known as the "king of cancers," is a highly lethal malignancy of the digestive system. Despite improvements in surgical methods and the development of new drugs, the prognosis for patients with pancreatic cancer has not improved substantially, with a five-year survival rate remaining below 9%. Pancreatic cancer research is therefore at a critical crossroads. Traditional chemotherapy regimens have largely reached their therapeutic limits, while targeted therapies and immunotherapies that have shown success in other cancers have failed in pancreatic cancer. This widespread phenomenon of therapeutic resistance highlights the existence of unique and still incompletely understood biological mechanisms underlying treatment failure.

This Special Issue aims to bring together cutting-edge basic research and innovative translational studies to comprehensively explore the multidimensional mechanisms of therapeutic resistance in pancreatic cancer and to investigate potential strategies for overcoming them. It will provide a panoramic view of resistance, addressing molecular mechanisms, the tumor microenvironment (TME), metabolism, and immunity. The ultimate goal is to bridge basic research, clinical application, and drug development, fostering a translational research framework that can drive the discovery of actionable strategies to improve therapeutic outcomes in pancreatic cancer.

Topics of interest include, but are not limited to:

● The role of the TME in therapeutic resistance in pancreatic cancer;

● Mechanisms of immune resistance in pancreatic cancer and strategies for remodeling the immune landscape;

● From monotherapy to multimodal approaches: combination therapies targeting multiple resistance mechanisms;

● Cell plasticity and reversible resistance driven by epithelial-mesenchymal transition (EMT);

● Repurposing existing drugs: the potential of statins, metformin, and other agents in overcoming therapeutic resistance in pancreatic cancer.

Pancreatic cancer, therapeutic resistance, immune evasion, metabolic reprogramming, combination therapy