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Subspecialties Oncology, Neurology

Shake off the Nerves

It is well known that perineural invasion (PNI) – the invasion of cancer to the space surrounding the nerves – can occur in solid tumors. Recently, it has been discovered that blocking nerve–tumor communication could improve patient outcomes, but what promotes this communication – and could we block it? Researchers are interrogating this possibility by looking into the genes and molecules responsible for the interaction between different cancers and nerves (1).

“Research has shown that tumor nerves, in different ways, ‘strengthen’ the tumor,” says Sara Wilson, Associate Professor at the Department of Integrative Medical Biology at Umeå University, Sweden. Cancer animal models have shown the potential advantages of using chemicals to interrupt nerve signals to the diseased organ, Wilson explains. The improvements differed depending on the cancer type and nerve but, overall, blocking the nerves either with chemicals or surgery reduced the likelihood of tumors forming in the first place, reduced tumor growth and recurrence, mitigated metastasis, and gave a better response to chemotherapy (2). Further, scientists noticed that, in patients with gastric cancer, the chance of recurrence was reduced when the vagus nerve was cut (3). Although this is promising, Wilson notes that “organs need nerves for normal function – so the therapy would need to be selective.”

Wilson and her team used bioinformatics to analyze genes of different cancers with a high density of tumor nerves and PNI, including head and neck, breast, prostate, pancreatic, and cholangiocarcinoma cancers. The most important finding was that the tumor and tumor microenvironments could be important sources of signals for nerve–tumor interactions including PNI, nerve plasticity, and neural tropism in a wide range of solid tumors throughout the body. “Interestingly, we also found that a group of genes which normally instruct nerves to develop during embryonic development – neurodevelopmental genes – were abnormal in the cancers analyzed,” says Wilson. “It’s as if the tumors reactivate the system normally used by embryonic neurons to develop and hijack it to provoke abnormal growth of the organ’s nerves during cancer.”

At the moment, the research is still at the preclinical stage. “The next phase will be about understanding if and how the genes we found are regulating nerve–tumor communication and finding ways to block them with chemical compounds,” states Wilson. “We then want to investigate if these chemicals will slow down cancer in animal models.” 

Credit: Lymphocytes in the blood by Juan Gaertner sourced from, Nerve Cells Neurons Nervous System by Colin Behrens sourced from

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  1. L M González-Castrillón et al., Front Genet (2023). PMID: 7719704.
  2. AH Zahalka, PS Frenette,Nat Rev Cancer, 20, 143 (2020). Available from: 
  3. CM Zhao et al., Sci Transl Med, 6 (2014). PMID: 25143365
About the Author
Georgia Hulme

Associate Editor for the Pathologist

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