Overcoming therapy resistance in pancreatic cancer: challenges and emerging strategies

Pancreatic cancer (PC) is one of the deadliest types of cancer, with a 5-year survival rate of ∼12.5 %. It is expected to become the second leading cause of cancer-related deaths by 2030. Despite recent advances in treatment options by the advent of various targeted and immunotherapies, their benefits have not been actualized for PC patients and chemotherapy remains the mainstay systemic therapeutic option for these patients. However, the majority of PC tumors have a highly chemo-resistant phenotype, leading to therapeutic failure. This review provides a comprehensive overview of the established mechanisms related to chemoresistance in PC and provides insight into emerging theories, including the potential role of the microbiome in modulating therapeutic responsiveness. It further discusses potential opportunities to explore to overcome this critical clinical problem.