Targeting sensory nerves in the tumor microenvironment: a new vulnerability in cancer therapy

TL;DR

This review explores how sensory nerves in the tumor environment contribute to cancer progression and highlights new strategies to target these nerves for cancer therapy.

Contribution

The paper synthesizes current knowledge on sensory nerve roles in the tumor microenvironment and emerging therapeutic strategies.

Findings

Sensory nerves in the tumor microenvironment promote cancer progression through complex interactions.

Targeting sensory nerves presents a novel therapeutic strategy in cancer treatment.

Neurotransmitters and neuropeptides from sensory nerves influence tumor hallmarks like proliferation and metastasis.

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.

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