Neuropathic Changes in Pancreatic Cancer

Academic Background

Pancreatic cancer is one of the most lethal cancers today, characterized by late diagnosis and high aggressiveness. Despite some progress in diagnosis and treatment in recent years, the five-year survival rate for pancreatic cancer remains extremely low, at only around 12%. The pathogenesis of pancreatic cancer is complex, involving genetic mutations, alterations in the tumor microenvironment, and the involvement of the nervous system. In recent years, increasing research has shown that the nervous system plays an important role in the initiation, progression, and metastasis of pancreatic cancer. Pancreatic cancer not only affects the local nervous system, leading to pathological changes such as neural hyperplasia, neural remodeling, and perineural invasion, but also influences the central nervous system (CNS) through specific molecules and cell types, causing symptoms such as pain, appetite suppression, and cognitive dysfunction. Additionally, chemotherapy-induced neuropathy is a common complication in pancreatic cancer patients, significantly impacting their quality of life. Therefore, a deeper understanding of the interactions between pancreatic cancer and the nervous system not only helps to reveal the mechanisms of pancreatic cancer pathogenesis but may also provide important clues for the development of novel therapeutic strategies.

Source of the Paper

This review paper was co-authored by Luju Jiang, Shuqi Cai, Zheqi Weng, Shan Zhang, and Shu-Heng Jiang, and was published in the February 2025 issue of Trends in Neurosciences. The authors are affiliated with the Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University. Their research focuses on neuropathic changes in pancreatic cancer and their molecular mechanisms.

Paper Topic and Main Points

This review systematically summarizes the neuropathic changes in pancreatic cancer and their molecular mechanisms, while exploring potential intervention strategies targeting the interactions between pancreatic cancer and the nervous system. The main points of the paper include:

1. Local Neuropathic Changes in Pancreatic Cancer

Common local neuropathic changes in pancreatic cancer include axonogenesis, neural remodeling, perineural invasion, and pancreatic neuritis. These changes not only affect the initiation and progression of pancreatic cancer but may also lead to clinical symptoms such as pain. For example, perineural invasion is one of the main sources of pain in pancreatic cancer patients and is closely associated with postoperative recurrence.

Supporting Evidence:
- Studies have shown that the occurrence of perineural invasion is closely related to the neurotropism of pancreatic cancer cells.
- Experimental models have demonstrated that pancreatic cancer cells can promote axonogenesis by releasing molecules such as nerve growth factor (NGF), thereby accelerating tumor growth and spread.

2. Impact of Pancreatic Cancer on the Central Nervous System

Pancreatic cancer not only affects the local nervous system but also influences the central nervous system through cancer cell-intrinsic factors or systemic factors, particularly in the context of cancer cachexia. Common CNS symptoms in pancreatic cancer patients include appetite suppression and cognitive decline.

Supporting Evidence:
- Research has shown that pancreatic cancer cells can activate astrocytes in the CNS by releasing cytokines such as IL-6, thereby affecting neural function.
- In pancreatic cancer patients with cachexia, significant changes in cholinergic and glutamatergic metabolic pathways in the CNS have been observed, which may contribute to cognitive dysfunction.

3. Chemotherapy-Induced Neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect in pancreatic cancer patients, primarily manifested as sensory abnormalities, pain, and nerve damage. Commonly used chemotherapy drugs such as oxaliplatin and paclitaxel are the main causes of CIPN.

Supporting Evidence:
- Studies have shown that chemotherapy drugs induce peripheral neuropathy by altering ion channels, increasing neuronal excitability, and affecting the gut microbiota.
- Clinical trials have demonstrated that drugs such as duloxetine have some efficacy in alleviating chemotherapy-induced neuropathic pain.

4. Neural Dependence and Therapeutic Potential in Pancreatic Cancer

The neural dependence mechanisms in pancreatic cancer provide important clues for the development of novel therapeutic strategies. Targeting the nervous system through interventions such as inhibiting the NGF signaling pathway or using β-blockers may help suppress tumor growth and alleviate pain.

Supporting Evidence:
- Experimental models have shown that inhibiting the NGF signaling pathway significantly reduces neural invasion and tumor growth in pancreatic cancer.
- Retrospective studies have indicated that long-term use of β-blockers improves the survival rate of pancreatic cancer patients.

Significance and Value of the Paper

This review comprehensively summarizes the various forms of neuropathic changes in pancreatic cancer and their molecular mechanisms, revealing the critical role of the nervous system in the pathogenesis and progression of pancreatic cancer. The paper not only provides new perspectives for understanding the pathophysiological mechanisms of pancreatic cancer but also offers a theoretical foundation for developing therapeutic strategies targeting the nervous system. Additionally, the paper discusses chemotherapy-induced neuropathy and its management strategies, providing important references for improving the quality of life of pancreatic cancer patients.

Highlights

1. Multidimensional Analysis: The paper provides a comprehensive analysis from multiple perspectives, including local neuropathic changes, CNS impact, and chemotherapy-induced neuropathy, offering an in-depth understanding of the interactions between pancreatic cancer and the nervous system.
   
2. Potential Therapeutic Targets: The paper proposes a series of potential intervention strategies, such as targeting the NGF signaling pathway and using β-blockers, providing new directions for pancreatic cancer treatment.
   
3. Clinical Relevance: The paper not only focuses on basic research but also integrates clinical practice, discussing chemotherapy-induced neuropathy and its management strategies, which hold significant clinical application value.

Through this review, researchers and clinicians can better understand the complex relationship between pancreatic cancer and the nervous system, providing strong theoretical support for future research and treatment.