Neurons in the tumor microenvironment release
neurotransmitters,
neuroligins,
chemokines, soluble
growth factors, and membrane-bound
growth factors that solid
tumors leverage to drive their own survival and spread.
Tumors express nerve-specific
growth factors and
microRNAs that support local neurons and guide neuronal growth into
tumors. The development of feed-forward relationships between
tumors and neurons allows
tumors to use the perineural space as a sanctuary from
therapy.
Tumor denervation slows
tumor growth in animal models, demonstrating the innervation dependence of growing
tumors. Further in vitro and in vivo experiments have identified many of the secreted signaling molecules (e.g.,
acetylcholine,
nerve growth factor) that are passed between neurons and
cancer cells, as well as the major signaling pathways (e.g., MAPK/EGFR) involved in these trophic interactions. The molecules involved in these signaling pathways serve as potential
biomarkers of disease. Additionally, new treatment strategies focus on using small molecules, receptor agonists, nerve-specific toxins, and surgical interventions to target
tumors, neurons, and immune cells of the tumor microenvironment, thereby severing the interactions between
tumors and surrounding neurons. This article discusses the mechanisms underlying the trophic relationships formed between neurons and
tumors and explores the emerging
therapies stemming from this work.