Mini-review: Trophic interactions between cancer cells and primary afferent neurons

Neurosci Lett. 2021 Feb 16;746:135658. doi: 10.1016/j.neulet.2021.135658. Epub 2021 Jan 19.


Cancer neurobiology is an emerging discipline that inevitably unfurls new perspectives in oncology. The role that nerves play in cancer progression resonates with the long-reported dependency of tumors on neuro-molecular mechanisms that remain insufficiently elucidated. Whereas interactions between neurotrophic growth factors and receptors have been heavily studied in the nervous system, their expression in cancers and their impact on tumor cell growth and metastasis through their corresponding signaling pathways has been undervalued. Accumulating evidence suggests that trophic factors released by nerves strongly influence tumor development and that this neural contribution appears to not only play a stimulatory role but also function as an essential part of the tumor's microenvironment. This bidirectional communication between proliferating cells and tumor-infiltrating nerves drives axonogenesis and tumor growth and migration. Acquiring a better understanding of the trophic interactions between primary afferent neurons and invading tumors will guide clinically actionable strategies to prevent tumor-associated axonogenesis, disrupting the chemical crosstalk between neurons and tumors and ultimately decreasing tumor growth and spread.

Keywords: Cancer progression; Neurotrophic growth; Tumor microenvironment; microRNA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Neoplasm Metastasis / pathology
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neurons, Afferent / metabolism*
  • Neurons, Afferent / pathology
  • Tumor Microenvironment / physiology*


  • Intercellular Signaling Peptides and Proteins