Repurposing EGFR Inhibitors for Oral Cancer Pain and Opioid Tolerance.
María Daniela SantiMorgan ZhangNaijiang LiuChi T VietTongxin XieDane D JensenMoran AmitHui-Lin Pan 潘惠麟Yi YePublished in: Pharmaceuticals (Basel, Switzerland) (2023)
Oral cancer pain remains a significant public health concern. Despite the development of improved treatments, pain continues to be a debilitating clinical feature of the disease, leading to reduced oral mobility and diminished quality of life. Opioids are the gold standard treatment for moderate-to-severe oral cancer pain; however, chronic opioid administration leads to hyperalgesia, tolerance, and dependence. The aim of this review is to present accumulating evidence that epidermal growth factor receptor (EGFR) signaling, often dysregulated in cancer, is also an emerging signaling pathway critically involved in pain and opioid tolerance. We presented preclinical and clinical data to demonstrate how repurposing EGFR inhibitors typically used for cancer treatment could be an effective pharmacological strategy to treat oral cancer pain and to prevent or delay the development of opioid tolerance. We also propose that EGFR interaction with the µ-opioid receptor and glutamate N-methyl-D-aspartate receptor could be two novel downstream mechanisms contributing to pain and morphine tolerance. Most data presented here support that repurposing EGFR inhibitors as non-opioid analgesics in oral cancer pain is promising and warrants further research.
Keyphrases
- chronic pain
- pain management
- epidermal growth factor receptor
- small cell lung cancer
- neuropathic pain
- tyrosine kinase
- public health
- signaling pathway
- advanced non small cell lung cancer
- squamous cell carcinoma
- machine learning
- spinal cord injury
- spinal cord
- electronic health record
- oxidative stress
- cell proliferation
- big data
- young adults
- drug induced
- deep learning
- global health
- binding protein