Sensory Nerve-Tumor Interplay: Mechanisms and Therapeutic Targets in Head and Neck Cancer

Head and neck cancer (HNC) represents a significant global health challenge, characterized by aggressive local invasion, frequent recurrence, and poor survival rates. Beyond its physical burden, HNC severely impacts patients’ quality of life, often causing debilitating pain and functional impairments. Recent breakthroughs in cancer neuroscience have revealed that the peripheral nervous system is not a passive bystander but an active participant within the tumor microenvironment. A seminal study demonstrated that under immune pressure, cancer cells can hijack sensory nerves to establish an inter-organ neuroimmune circuit. This review aims to synthesize current knowledge on the multifaceted roles of sensory nerves in HNC progression, pain modulation, and immune regulation. It will provide an in-depth analysis of the underlying molecular mechanisms and explore the translational potential of targeting these neural pathways—such as repurposing CGRP receptor inhibitors—to develop novel strategies that concurrently inhibit tumor progression and alleviate cancer-induced pain.