Nerves in gastrointestinal cancer: from mechanism to modulations

Nathalie Vaes, Musa Idris, Werend Boesmans, Maria M. Alves, Veerle Melotte*

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

8 Citations (Scopus)


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 ~19% of all cancer cases and ~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.

Original languageEnglish
Pages (from-to)768-784
Number of pages17
JournalNature Reviews Gastroenterology and Hepatology
Issue number12
Early online date2 Sept 2022
Publication statusPublished - Dec 2022

Bibliographical note

Funding Information:
The authors’ work is financially supported by VENI-NWO grant (016.186.124) obtained by V.M., the Kootstra Talent Fellowship grant (Maastricht University) obtained by N.V. and the Hestia – NWO grant (VidW.1154.18.045) obtained by M.I and V.M.

Publisher Copyright:
© 2022, Springer Nature Limited.


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