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The contribution of the nervous system in the cancer progression

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Cancer progression is driven by genetic mutations, environmentalfactors, and intricate interactions within the tumor microenvironment(TME). The TME comprises of diverse cell types,such as cancer cells, immune cells, stromal cells, and neuronalcells. These cells mutually influence each other through variousfactors, including cytokines, vascular perfusion, and matrixstiffness. In the initial or developmental stage of cancer, neurotrophicfactors such as nerve growth factor, brain-derived neurotrophicfactor, and glial cell line-derived neurotrophic factorare associated with poor prognosis of various cancers by communicatingwith cancer cells, immune cells, and peripheralnerves within the TME. Over the past decade, research has beenconducted to prevent cancer growth by controlling the activationof neurotrophic factors within tumors, exhibiting a novelattemt in cancer treatment with promising results. More recently,research focusing on controlling cancer growth through regulationof the autonomic nervous system, including the sympatheticand parasympathetic nervous systems, has gained significantattention. Sympathetic signaling predominantly promotestumor progression, while the role of parasympathetic signalingvaries among different cancer types. Neurotransmitters releasedfrom these signalings can directly or indirectly affect tumor cellsor immune cells within the TME. Additionally, sensory nervesignificantly promotes cancer progression. In the advanced stageof cancer, cancer-associated cachexia occurs, characterized bytissue wasting and reduced quality of life. This process involvesthe pathways via brainstem growth and differentiation factor15-glial cell line-derived neurotrophic factor receptor alpha-likesignaling and hypothalamic proopiomelanocortin neurons. Ourreview highlights the critical role of neurotrophic factors aswell as central nervous system on the progression of cancer,offering promising avenues for targeted therapeutic strategies.

Abstract

Cancer progression is driven by genetic mutations, environmentalfactors, and intricate interactions within the tumor microenvironment(TME). The TME comprises of diverse cell types,such as cancer cells, immune cells, stromal cells, and neuronalcells. These cells mutually influence each other through variousfactors, including cytokines, vascular perfusion, and matrixstiffness. In the initial or developmental stage of cancer, neurotrophicfactors such as nerve growth factor, brain-derived neurotrophicfactor, and glial cell line-derived neurotrophic factorare associated with poor prognosis of various cancers by communicatingwith cancer cells, immune cells, and peripheralnerves within the TME. Over the past decade, research has beenconducted to prevent cancer growth by controlling the activationof neurotrophic factors within tumors, exhibiting a novelattemt in cancer treatment with promising results. More recently,research focusing on controlling cancer growth through regulationof the autonomic nervous system, including the sympatheticand parasympathetic nervous systems, has gained significantattention. Sympathetic signaling predominantly promotestumor progression, while the role of parasympathetic signalingvaries among different cancer types. Neurotransmitters releasedfrom these signalings can directly or indirectly affect tumor cellsor immune cells within the TME. Additionally, sensory nervesignificantly promotes cancer progression. In the advanced stageof cancer, cancer-associated cachexia occurs, characterized bytissue wasting and reduced quality of life. This process involvesthe pathways via brainstem growth and differentiation factor15-glial cell line-derived neurotrophic factor receptor alpha-likesignaling and hypothalamic proopiomelanocortin neurons. Ourreview highlights the critical role of neurotrophic factors aswell as central nervous system on the progression of cancer,offering promising avenues for targeted therapeutic strategies.

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