The role of cancer cell-released extracellular vesicles: have we become closer to cancer pain treatment?

The effective management of cancer pain continues to be a challenge because of our limited understanding of cancer pain mechanisms and, in particular, how cancer cells interact with neurons to produce pain. In a study published in <i>Pain</i>, Inyang <i>et al.</i> used a mouse model of human papillomavirus (HPV1)-induced oropharyngeal squamous cell carcinoma to show a role for cancer cell-derived extracellular vesicles (cancer sEVs) in cancer pain. They found that inhibiting the release of sEVs reduced spontaneous and evoked pain behaviors, and that pain produced by sEVs is due to activation of TRPV1 channels. An innovative approach was the use of publicly available human RNA-sequencing data from unstimulated cultured human dorsal root ganglia (DRG) that were exposed to human head and neck squamous cell carcinoma (HNSCC)-derived sEVs to identify signaling pathways involved in the nascent translation associated with nociception. These studies further our understanding of functional interactions between cancer cells and neurons, and suggest an approach to identify novel targets for the treatment of cancer pain.