Drugs already approved to treat nerve pain and migraines may one day serve a new purpose: helping to slow the growth of bone cancer.
In a new study published in Proceedings of the National Academy of Sciences, researchers led by Johns Hopkins Medicine found that two medications—bupivacaine and rimegepant—not only reduced cancer-related pain in mice with osteosarcoma, but also slowed tumor growth and spread.
Osteosarcoma is a rare but aggressive bone cancer that most often affects children and young adults.
The disease is frequently accompanied by severe pain. Scientists have known that peripheral sensory nerves, which send signals from the body to the brain and spinal cord, can grow into these tumors.
However, this new research suggests those nerves do more than transmit pain—they may also help tumors grow.
The team focused on a signaling pathway involving three proteins: nerve growth factor (NGF), its receptor TrkA, and a molecule called calcitonin gene-related peptide (CGRP). These proteins are involved in communication between nerves and tumor cells.
In earlier research, the same group had shown that NGF-TrkA signaling helps promote healing after bone fractures by encouraging nerve and blood vessel growth. But in osteosarcoma, that same pathway appears to fuel tumor development.
In experiments using mice with osteosarcoma-like tumors, researchers genetically blocked TrkA activity. Mice with reduced NGF-TrkA signaling had much less nerve growth within their tumors. They also showed slower tumor progression, less cancer spread, and longer survival compared to untreated mice.
The researchers found that blocking this pathway also reduced tumor-associated macrophages—immune cells that can unintentionally help tumors grow and resist treatment by weakening the body’s anti-cancer response.
To confirm that similar processes occur in humans, the team examined tissue samples from people with osteosarcoma. These samples showed increased nerve and blood vessel growth linked to NGF-TrkA signaling, similar to what was seen in mice. They also studied nerve tissue from patients who experienced tumor-related pain and found increased CGRP activity and inflammation.
Based on these findings, the researchers tested whether drugs that block these nerve signals could make a difference. Bupivacaine, commonly used as a local anesthetic for nerve pain, and rimegepant, a migraine medication that blocks CGRP, both reduced nerve growth and blood vessel formation in tumors in mice. Importantly, the drugs also slowed tumor growth and spread.
Because both medications are already approved by the U.S. Food and Drug Administration, researchers believe they could potentially be repurposed more quickly than entirely new drugs. However, the findings are still based on laboratory studies in animals, and more research will be needed before testing in humans.
The team now plans to further investigate how peripheral nerves interact with tumors and how these signals can be safely targeted.
If future studies confirm these results, blocking nerve-tumor communication could become a promising new strategy for treating osteosarcoma—while also easing the severe pain the disease often causes.
