Researchers from Johns Hopkins Medicine and several partner institutions have discovered that two existing pain medications could help fight one of the most aggressive bone cancers — osteosarcoma.
The study, published in the Proceedings of the National Academy of Sciences (PNAS), found that the drugs bupivacaine and rimegepant not only eased severe cancer-related pain in mice but also slowed the tumor’s growth and spread.
Osteosarcoma is a malignant bone tumor that often develops in children and young adults. It causes intense pain because nerve cells, called peripheral afferent neurons, grow into and around the tumor.
These neurons normally carry sensory signals from the body to the brain and spinal cord, but in this case, they appear to help the cancer grow by stimulating nerve and blood vessel formation inside the tumor.
The research team led by Dr. Sowmya Ramesh, a postdoctoral fellow at Johns Hopkins University School of Medicine, discovered that bupivacaine — a common local anesthetic used for nerve pain — and rimegepant — a drug approved for migraines — could disrupt this harmful nerve-to-tumor communication.
Both drugs block the actions of three key proteins: calcitonin gene-related peptide (CGRP), tryptomyosin receptor kinase-A (TrkA), and nerve growth factor (NGF). Together, these proteins promote nerve growth (innervation) and new blood vessel formation (angiogenesis) inside tumors, creating an environment that helps the cancer thrive.
By blocking these proteins, the researchers found that both drugs reduced nerve and blood vessel formation in mouse models of osteosarcoma. More importantly, this also slowed tumor growth and spread. Dr. Ramesh explained that these results raise hope that drugs already approved for pain relief could be repurposed as new treatments for bone cancer.
Interestingly, this discovery takes a very different approach from the researchers’ previous work. Dr. Aaron James, senior author of the study and professor of pathology at Johns Hopkins, explained that his lab had earlier studied the same proteins for bone healing.
“In earlier experiments, we tried to increase NGF and TrkA activity to help bones heal after fractures,” James said. “But in the case of osteosarcoma, the goal is the exact opposite — to stop these signals to prevent tumor growth and nerve invasion.”
To better understand how sensory nerves affect tumor growth, the researchers used genetically modified mice in which TrkA signaling was blocked. The mice with inhibited NGF-TrkA signaling showed much less nerve growth inside their tumors, slower cancer spread, and longer survival times.
They also had fewer tumor-associated macrophages — immune cells that often promote tumor growth and make cancers more resistant to chemotherapy.
The team also analyzed tissue samples from human osteosarcoma patients and found evidence that NGF-TrkA signaling was active, leading to increased nerve and blood vessel growth similar to what was seen in the mice.
Samples of spinal cord–related neurons from patients who experienced tumor pain showed high levels of CGRP activity and inflammation, further linking these signals to both pain and cancer progression.
When researchers treated mice with bupivacaine and rimegepant, the drugs successfully reduced the amount of nerve and blood vessel growth within the tumors. This not only helped ease tumor pain but also limited the cancer’s ability to expand and spread. The results suggest that targeting nerve signaling in bone cancers could be a promising new therapeutic strategy.
Dr. Ramesh and her team now plan to study exactly how neurons interact with osteosarcoma cells and how their communication can be interrupted without harming healthy tissue.
If the findings can be confirmed in human trials, these common pain drugs could one day offer a double benefit — relieving the pain of osteosarcoma while also helping to slow the disease itself.
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The study is published in PNAS.
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