Pancreatic cancer remains one of the deadliest cancers, with survival rates showing little improvement over decades and projections placing it as the second leading cause of cancer deaths by 2030. Chemotherapy is essential for all patients, yet most tumors lacking BRCA1/2 or PALB2 mutations show resistance to cisplatin. Growing evidence suggests that targeting nuclear factor NF-κB, a key driver of cancer progression, could help overcome this chemoresistance and improve treatment outcomes.