Abstract
Gastrointestinal (GI) cancer is a formidable malignancy with significant morbidity and mortality rates. Recent studies have shed light on the complex interplay between the nervous system and the GI system, influencing various aspects of GI tumorigenesis, such as the malignance of cancer cells, the conformation of tumor microenvironment (TME), and the resistance to chemotherapies. The discussion in this review first focused on exploring the intricate details of the biological function of the nervous system in the development of the GI tract and the progression of tumors within it. Meanwhile, the cancer cell-originated feedback regulation on the nervous system is revealed to play a crucial role in the growth and development of nerve cells within tumor tissues. This interaction is vital for understanding the complex relationship between the nervous system and GI oncogenesis. Additionally, the study identified various components within the TME that possess a significant influence on the occurrence and progression of GI cancer, including microbiota, immune cells, and fibroblasts. Moreover, we highlighted the transformation relationship between non-neuronal cells and neuronal cells during GI cancer progression, inspiring the development of strategies for nervous system-guided anti-tumor drugs. By further elucidating the deep mechanism of various neuroregulatory signals and neuronal intervention, we underlined the potential of these targeted drugs translating into effective therapies for GI cancer treatment. In summary, this review provides an overview of the mechanisms of neuromodulation and explores potential therapeutic opportunities, providing insights into the understanding and management of GI cancers.