Targeting Neurons in the Osteosarcoma Microenvironment with Non-Opioid Analgesic Lipid Nanoparticles
Osteosarcoma is a type of bone cancer that begins in bone-forming cells. The conventional treatment strategy involves tumor resection and chemotherapeutic drugs. The 5-year survival rate is about 70% in patients with confined osteosarcoma; however, this regimen largely fails in patients with recurrence and/or when it spreads to other body parts. The prognosis for patients with metastatic disease is grim with an overall 5-year survival rate <20%. With these sobering statistics in mind, novel adjunctive therapies to reduce osteosarcoma disease progression, prolong the life expectancy of patients, and improve their quality of life are urgently needed. Bone pain is an extremely common presenting symptom for patients with bone tumors. Literature suggests that about two-thirds of nerve pain in cancer patients is related to tumor growth. As the tumor develops, nerve fibers in the bone are damaged, and the pain fibers become more sensitive, triggering spontaneous pain that is amplified. A detailed understanding of how tumor-induced bone pain is initiated is necessary. The present proposal will provide fundamental biological insights on how nerves regulate osteosarcoma disease progression and target these tumor-associated neurons using sustained delivery of bupivacaine, a drug that is already approved by the FDA for use as nerve blocker.
The goal of this project is to identify and target the nerves associated with the perception and transmission of pain signals in bone during the development of osteosarcoma, a type of bone cancer. Using a mouse model of osteosarcoma, we aim to sequentially investigate the mechanisms behind how pain signals are transmitted and perceived within the bone during cancer progression. This will eventually allow us to discover key pathways altered in cancer-induced bone pain. Next, in a translational effort, we seek to examine the potential use of bupivacaine that can act as a pain-reliever as well as novel method to reduce tumor growth. Ultimately, this research has the potential to improve our understanding of osteosarcoma and develop new strategies for treating bone cancer.