Treating Oral Cancer Pain with LRP1 Agonists
Abstract
Active military personnel and Veterans represent a large population of individuals suffering from chronic pain due to multiple types of traumatic injuries and disease, including oral cancer. Oral cancer is very common (four times more than the civilian) in our active military and Veteran populations. Pain is rated as the worst symptom, and patients have difficulty eating, drinking, and talking. Oral cancer pain is frequently accompanied by other psychosocial comorbidities such as anxiety, depression, fatigue, and sleep disorders. Unfortunately, existing treatments for chronic pain (i.e., opioids) are ineffective and associated with deleterious side effects, greatly worsening what is already the substantial burden of cancer. Our research program aims to understand the basic causes of chronic oral cancer pain, and to identify new treatments for chronic pain. We recently discovered a novel cell receptor system that has cell survival and anti-inflammatory properties. Activators of the receptor system reduced acute pain and prevented the development of chronic pain in our preclinical models. Our preliminary studies suggest that the mechanism of action includes regulating activities of specialized cells that support nerves, and inflammatory cells in keeping pain transmitting nerves healthy. Herein, we will test whether our receptor activators function in combination with specialized cells to antagonize inflammation and prevent oral cancer pain. Studies planning to test effects on pain behaviors and cellular and molecular mechanisms are underway. We also plan to identify novel populations of cells in tumor tissues that contribute to oral cancer pain. A consideration of great importance in this work is whether novel drugs that activate this receptor system can improve chronic pain such as oral cancer pain. This information is essential for the initiation of human clinical trials, and is consistent with our overarching research vision to understand the causes and develop effective treatments for chronic pain. This project will foster work in a new direction in oral cancer research while addressing a neglected issue that extracts an enormous human toll from our Soldiers and Veterans: chronic pain. Successful completion of this research program will add to our basic knowledge of cellular and molecular causes of pain, and could lead to the clinical implementation of an innovative new therapy for chronic pain based on the powerful biology.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210723
Entities
People
- Yi Ye
Organizations
- New York University
- United States Army