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Updated: Jan 31, 2026
A Brain Tumor/Organotypic Slice Co-culture System for Studying Tumor Microenvironment and Targeted Drug Therapies
Published on: November 7, 2015
Targeting sensory nerves in the tumor microenvironment: a new vulnerability in cancer therapy
Jun Jiang1,2, Zhe Xu3, Danyu Qu4
1Department of Urology, Xijing Hospital, Air Force Medical University, Xi'an, China.
Abstract:
Tumor innervation, the infiltration of nerves into the tumor microenvironment (TME), is increasingly recognized as a novel hallmark driving cancer progression and is associated with poor patient prognosis across various solid malignancies. This process is orchestrated by a complex, bidirectional crosstalk. Cancer and stromal cells release neurotrophic factors that induce axonogenesis or neurogenesis. In turn, the infiltrating nerves, particularly sensory nerves, secrete neurotransmitters, neuropeptides or form pseudo-synapse with tumor cells to facilitate cancer hallmarks, including sustained proliferation, invasion, metastasis, modulation of the anti-tumor immune response, and cancer plasticity. However, the specific contributions and underlying mechanisms of sensory nerve innervation in orchestrating malignancy remain incompletely elucidated. This review aims to synthesize the current understanding of the multifaceted roles of sensory neurons within the TME, detailing their intricate interactions with cancer and stromal cells, and highlighting the emerging therapeutic strategies that target the sensory nerve-tumor axis.
Insights
Tumor innervation, the infiltration of nerves into the tumor microenvironment, fuels cancer progression and poor prognosis. Sensory nerves within this microenvironment significantly contribute to malignancy via complex crosstalk with cancer and stromal cells.
Area of Science:
- Oncology
- Neuroscience
- Cancer Biology
Background:
- Tumor innervation, the presence of nerves within the tumor microenvironment (TME), is an emerging hallmark of cancer.
- This nerve infiltration is linked to poor patient prognosis in various solid tumors.
- The interaction between nerves and tumors involves complex bidirectional communication.
Purpose of the Study:
- To review the current understanding of sensory neuron roles in the TME.
- To detail the interactions between sensory nerves, cancer cells, and stromal cells.
- To highlight therapeutic strategies targeting the sensory nerve-tumor axis.
Main Methods:
- Literature review and synthesis of existing research.
- Analysis of preclinical and clinical studies on tumor innervation.
- Identification of key molecular mechanisms and signaling pathways.
Main Results:
- Cancer and stromal cells release neurotrophic factors, promoting nerve growth (axonogenesis/neurogenesis).
- Sensory nerves secrete neurotransmitters and neuropeptides, influencing cancer hallmarks like proliferation, invasion, metastasis, immune response, and plasticity.
- Specific mechanisms of sensory nerve involvement in malignancy are still under investigation.
Conclusions:
- Sensory nerves play a multifaceted role in orchestrating cancer progression within the TME.
- Targeting the sensory nerve-tumor axis presents a promising therapeutic avenue.
- Further research is needed to fully elucidate the underlying mechanisms.
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