Abstract
As the field of cancer neuroscience expands, the strategic targeting of interactions between neurons, cancer cells and other elements in the tumour microenvironment represents a potential paradigm shift in cancer treatment, comparable to the advent of our current understanding of tumour immunology. Cancer cells actively release growth factors that stimulate tumour neo-neurogenesis, and accumulating evidence indicates that tumour neo-innervation propels tumour progression, inhibits tumour-related pro-inflammatory cytokines, promotes neovascularization, facilitates metastasis and regulates immune exhaustion and evasion. In this Review, we give an up-to-date overview of the dynamics of the tumour microenvironment with an emphasis on tumour innervation by the peripheral nervous system, as well as current preclinical and clinical evidence of the benefits of targeting the nervous system in cancer, laying a scientific foundation for further clinical trials. Combining empirical data with a biomarker-driven approach to identify and hone neuronal targets implicated in cancer and its spread can pave the way for swift clinical integration.
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Acknowledgements
M.A.’s work is supported by the NIH/NIDCR (R01DE032018); NIH/NCI (R37CA242006); the University of Texas MD Anderson Cancer SPORE in Melanoma (P50-CA093459), Jim Mulva Foundation and the NCI Cancer Moonshot programme. S.T.’s work is supported by the Canadian Institutes of Health Research (407016, 461274, 461275), Canadian Foundation for Innovation (44135), Knut and Alice Wallenberg Foundation (KAW 2021.0141, KAW 2022.0327), Swedish Research Council (2022-01661), Natural Sciences and Engineering Research Council of Canada (RGPIN-2019-06824) and NIH/NIDCR (R01DE032712).
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D.Y., B.M., F.O.G.-N. and M.A. researched data for the article and contributed substantially to discussion of the content. All authors wrote the article and reviewed and/or edited the manuscript before submission.
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Glossary
- Axoplasm
-
The fluid interior of the axon of a neuron, which contains cellular components and molecules essential for axon function.
- High-plex protein labelling
-
An advanced technique that allows researchers to simultaneously tag and measure more than 100 different proteins in a single sample.
- Immortal time bias
-
A potential source of error in cohort studies in which the analysis incorrectly includes a period during which the outcome of interest cannot occur for the exposed group, leading to biased results.
- Myelin sheath
-
A fatty insulating layer that surrounds nerve fibres that enhances the speed of electrical impulse transmission along neurons.
- NETosis
-
A type of cell death that is characterized by the release of decondensed chromatin and granular contents to the extracellular space, also known as neutrophil extracellular traps (NETs).
- Neurotrophic
-
Describes a substance that promotes the survival, growth and function of neurons in the nervous system.
- Optogenetics
-
An innovative neuroscience technique that uses light-sensitive proteins to control and study the activity of specific neurons in living tissue.
- ROBO
-
A family of proteins that have a crucial role in guiding the growth and direction of axons during nervous system development.
- Slit proteins
-
Signalling molecules that interact with ROBO receptors to regulate axon guidance and cell migration in the nervous system.
- Somatosensory
-
Relating to the sensory system that detects and processes information about touch, temperature, body position and pain.
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Yaniv, D., Mattson, B., Talbot, S. et al. Targeting the peripheral neural-tumour microenvironment for cancer therapy. Nat Rev Drug Discov 23, 780–796 (2024). https://doi.org/10.1038/s41573-024-01017-z
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DOI: https://doi.org/10.1038/s41573-024-01017-z
