Pancreatic ductal adenocarcinoma (PDAC) is the most malignant form of pancreatic cancer and has the highest mortality among all major cancers. However, there are still many unknowns in PDAC and many treatments that work for other cancers are ineffective against PDAC. Therefore, new therapies or combination therapies are needed to increase patient survival. In order to develop such treatments, alternative aspects of PDAC must be considered. One factor that has been identified but requires further consideration in PDAC development and progression is the role of stress-related biomolecules. Neuropsychiatric and neurodegenerative conditions have been found to be strongly associated with PDAC. This comorbidity and the dysregulation of stress-related biomolecules in both PDAC and neurological conditions may indicate a new drug target for treating PDAC. Neurotransmitters released by the brain have been shown to promote PDAC's tumor microenvironment (TME)–modulating angiogenesis, immunosuppression, and preventing apoptosis. This systematic review summarizes the findings of research studies investigating the consequences of cancer-reprogrammed neurotransmitters and the comorbidity between PDAC and neurological disorders. Based on the studies reviewed here, there exists a positive potential benefit to combination therapies that include traditional chemotherapeutic agents and existing neuropsychiatric medications. These findings highlight a gap in knowledge in the field of PDAC that requires further investigation.
Zhao et al. (2026) studied this question.