How Nerve Signals and Neuropeptides Help Cancer Spread to Bones | Research

The takeaway

Neuropeptides like substance P and CGRP shape the bone environment in ways that can promote cancer metastasis, opening new therapeutic targets.

Dual role
Substance P and CGRP affect both bone-remodeling cells and immune cells in the metastatic niche

What the researchers found

Neuropeptides such as substance P and CGRP exert dual effects on bone-remodeling cells and immune populations, directly shaping the metastatic niche that allows cancer cells to grow in bone.

Why it matters

Understanding how neuropeptides influence the bone microenvironment could lead to new combination therapies that disrupt neural support for metastatic cancer, potentially improving outcomes for patients with bone metastases.

How the study worked

Narrative review synthesizing preclinical and clinical evidence on bone innervation, tumor-induced neural remodeling, and neuro-immune-osteoclast interactions in bone metastasis.

What this study cannot tell us

As a narrative review, it does not provide new experimental data. Many of the proposed therapeutic strategies are based on preclinical models, and the spatial mapping of nerve-tumor interfaces in humans remains incomplete.

How to read the evidence

Narrative review summarizing mostly preclinical evidence with some clinical observations; no new primary data presented.

When this study was published

Published in 2025, reflecting current understanding of the neuro-bone axis in cancer.

The bigger picture

This work bridges oncology, neuroscience, and bone biology by showing that neural signaling—particularly through neuropeptides—is a critical but overlooked driver of bone metastasis. It positions neuromodulatory strategies as promising adjuncts to existing cancer therapies.

Questions still open

Can beta-blockers or neurotrophin inhibitors meaningfully slow bone metastasis progression in clinical trials?
How do substance P and CGRP levels differ between metastatic and healthy bone tissue?
Could targeted nerve ablation techniques selectively disrupt tumor-supporting neural circuits without impairing normal bone function?

Common questions

What are substance P and CGRP and why do they matter for bone metastasis?

Substance P and CGRP are neuropeptides released by nerve fibers in bone. They influence both bone-remodeling cells and immune cells, and emerging evidence suggests they help create conditions favorable for cancer growth in bone.

Could targeting nerves in bone help treat cancer?

Potentially, yes. This review highlights that beta-blockers, neurotrophin inhibitors, and targeted nerve ablation could disrupt neural support for metastatic tumors, though clinical trials are still needed.

Read the original research

The Neuro-Bone Axis in Metastatic Progression: Innervation, Neuro-Immune-Osteoclast Crosstalk, and Therapeutic Opportunities.

Biology, 15(4)

View on PubMed ↗Publisher’s paper ↗

Citation

Bakir, Mohamad; Dabaliz, Alhomam; Raddaoui, Mohammed; Fatash, Hala; Elsaadany, Nourhan; AlKattan, Wael; Mohammad, Khalid Said. (2026). The Neuro-Bone Axis in Metastatic Progression: Innervation, Neuro-Immune-Osteoclast Crosstalk, and Therapeutic Opportunities.. Biology, 15(4). https://doi.org/10.3390/biology15040364