Nerves in gastrointestinal cancer: from mechanism to modulations

Maintenance of gastrointestinal health is challenging as it requires balancing multifaceted processes within the highly complex and dynamic ecosystem of the gastrointestinal tract. Disturbances within this vibrant environment can have detrimental consequences, including the onset of gastrointestinal cancers. Globally, gastrointestinal cancers account for similar to 19% of all cancer cases and similar to 22.5% of all cancer-related deaths. Developing new ways to more readily detect and more efficiently target these malignancies are urgently needed. Whereas members of the tumour microenvironment, such as immune cells and fibroblasts, have already been in the spotlight as key players of cancer initiation and progression, the importance of the nervous system in gastrointestinal cancers has only been highlighted in the past few years. Although extrinsic innervations modulate gastrointestinal cancers, cells and signals from the gut's intrinsic innervation also have the ability to do so. Here, we shed light on this thriving field and discuss neural influences during gastrointestinal carcinogenesis. We focus on the interactions between neurons and components of the gastrointestinal tract and tumour microenvironment, on the neural signalling pathways involved, and how these factors affect the cancer hallmarks, and discuss the neural signatures in gastrointestinal cancers. Finally, we highlight neural-related therapies that have potential for the management of gastrointestinal cancers.

Automated summary

Maintaining gastrointestinal health is challenging due to the complex and dynamic nature of the gastrointestinal tract. Disturbances in this environment can lead to gastrointestinal cancers, which account for a significant proportion of cancer cases and deaths worldwide. While the role of the tumor microenvironment has been extensively studied, the importance of the nervous system in gastrointestinal cancers has only recently been recognized. This article sheds light on the neural influences during gastrointestinal carcinogenesis, focusing on interactions between neurons and components of the gastrointestinal tract and tumor microenvironment, neural signaling pathways, and the impact on cancer hallmarks. Neural-related therapies for gastrointestinal cancer management are also discussed.