TY - JOUR
T1 - Interrupting neuron—tumor interactions to overcome treatment resistance
AU - Hunt, Patrick J.
AU - Kabotyanski, Katherine E.
AU - Calin, George A.
AU - Xie, Tongxin
AU - Myers, Jeffrey N.
AU - Amit, Moran
N1 - Funding Information:
Funding: This work was funded by the American Heart Association under award number 20PRE35040011 and by BRASS: Baylor Research Advocates for Student Scientists (PJH). This work was additionally funded by the National Institutes of Health (NIH) under award number T32GM136611 (KEK). This work was additionally funded by the Moon Shots Program (MA). Finally, this work was funded by the NIH/National Cancer Institute under award numbers P30CA016672 and 1R37CA242006 (MA).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/12
Y1 - 2020/12
N2 - 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.
AB - 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.
KW - Cancer progression
KW - MicroRNA
KW - Neurotrophic growth
KW - Tumor microenvironment
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U2 - 10.3390/cancers12123741
DO - 10.3390/cancers12123741
M3 - Review article
C2 - 33322770
AN - SCOPUS:85097831829
SN - 2072-6694
VL - 12
SP - 1
EP - 19
JO - Cancers
JF - Cancers
IS - 12
M1 - 3741
ER -