Neural influences in colorectal cancer progression and therapeutic strategies

作者：Zhibin Zeng, Shirong Cai, C. Ye, T.-F. Li, Yan Tian, Enyuan Liu, Junbin Cai, Xiaojun Yuan, Heng Yang, Quanqi Liang, Kaishu Li, Cui Peng · 发表于：International Journal of Colorectal Disease · 年份：2025 · DOI：10.1007/s00384-025-04887-w · 被引用次数：10 · 研究领域：Cancer, Stress, Anesthesia, and Immune Response、Cancer Cells and Metastasis、Advanced Breast Cancer Therapies

PURPOSE: This review aims to elucidate the neural mechanisms driving colorectal cancer (CRC) growth, metastasis, and therapeutic resistance, summarizing the roles of neurotransmitters, neurotrophic factors, and neural signaling in carcinogenesis. It further explores therapeutic strategies targeting neural dependencies in CRC. METHODS: A comprehensive PubMed search was conducted using the keywords colorectal cancer and tumor innervation, focusing on studies published between 2000 and 2024. The review synthesizes evidence across four domains: neurotransmitter-receptor interactions, gut-brain-microbiota axis dynamics, neuroimmune modulation, and neural regulation of cancer stem cells, discussing their collective impact on CRC pathophysiology. RESULTS: Neural innervation significantly influences CRC progression. For instance, the neurotransmitter serotonin promotes tumor growth and metastasis via paracrine and autocrine stimulation, while neurotrophic mediators like nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) activate oncogenic signaling through receptor tyrosine kinases (RTKs). Downstream pathways, such as Wnt/β-catenin signaling, are modulated by neural inputs, underscoring CRC's neurodevelopmental dependency and highlighting their potential as therapeutic targets. CONCLUSION: Neural mechanisms are pivotal in CRC progression, revealing novel therapeutic avenues. Strategies targeting neurotransmitter synthesis, neurotrophic signaling, or neuroimmune cr...