Peripheral, central, and chemotherapy-induced neuropathic changes in pancreatic cancer

In pancreatic cancer, significant alterations occur in the local nervous system, including axonogenesis, neural remodeling, perineural invasion, and perineural neuritis. Pancreatic cancer can impact the central nervous system (CNS) through cancer cell-intrinsic factors or systemic factors, particularly in the context of cancer cachexia. These peripheral and central neuropathic changes exert substantial influence on cancer initiation and progression. Moreover, chemotherapyinduced neuropathy is common in pancreatic cancer, causing peripheral nerve damage and cognitive dysfunction. Targeting the crosstalk between pancreatic cancer and the nervous system, either peripherally or centrally, holds promise in cancer treatment, pain relief, and improved quality of life. Here, we summarize recent findings on the molecular mechanisms behind these neuropathic changes in pancreatic cancer and discuss potential intervention strategies.