Targeting the Nerve-Cancer Circuit.

Area of Science:

• Oncology
• Neuroscience
• Cancer Biology

Background:

• The tumor microenvironment (TME) is influenced by nerve fibers, impacting cancer progression.
• Understanding the molecular mechanisms of cancer-nerve interactions is crucial for developing novel therapies.

Purpose of the Study:

• To investigate the role of specific neuronal subtypes and molecular signals in mediating cancer-nerve interactions.
• To identify a generalizable pathway for targeting cancer growth and metastasis.

Main Methods:

• Analysis of tumor innervation across various cancer types.
• Investigation of the functional connectivity of intratumoral nerve fibers.
• Assessment of the role of substance P and its receptor, neurokinin 1 receptor (NK1R), in tumor cell proliferation and migration.

Main Results:

• Tumors are densely innervated, primarily by transient receptor potential cation channel subfamily V member 1 positive (TRPV1+) sensory fibers, irrespective of tumor type or location.
• Intratumoral nerve fibers exhibit functional connectivity, potentially increasing electrical activity within the tumor.
• Substance P, released by intratumoral fibers, activates NK1R on tumor cells, promoting tumor proliferation and migration.

Conclusions:

• A conserved molecular pathway involving TRPV1+ sensory fibers, substance P, and NK1R mediates cancer-nerve interactions.
• Targeting this pathway offers a potential strategy for inhibiting tumor growth and metastasis across diverse cancer types.