FDA-Approved Pain Drugs and Novel Compounds Show Promise in Bone Cancer Models

Recent experimental studies have identified several drugs and compounds that reduced tumor progression and pain in mouse models of bone cancer.

Research involving FDA-approved pain medications bupivacaine and rimegepant found that these drugs decreased nerve and blood vessel development within osteosarcoma tumors in mice. In these models, the drugs also slowed the progression of the tumors, indicating effects beyond their approved uses for pain management.

Bupivacaine and rimegepant were observed to work by blocking specific signaling pathways, including CGRP, TrkA, and NGF, which are involved in communication between neurons and tumor cells. By interfering with these pathways, the drugs reduced both tumor innervation and the formation of new blood vessels within the tumor environment.

Separate studies using STING agonists in mouse models of bone cancer demonstrated reductions in cancer-induced pain and improvements in movement. These compounds also led to decreased bone destruction and a lower overall tumor burden in the animals tested.

What the numbers show

• Bupivacaine and rimegepant reduced nerve and blood vessel growth in mouse osteosarcoma models
• STING agonists were administered systemically in multiple mouse studies
• GPR37 activation effects were absent in Gpr37-deficient mice

STING agonists provided both immediate and longer-term benefits in these models. The compounds produced acute pain relief through direct effects on neurons and contributed to longer-term improvements by acting on bone-resorbing cells and immune system components.

Another line of research focused on the activation of GPR37, a receptor involved in nervous system signaling. Compounds such as neuroprotectin D1 and artesunate activated GPR37 in mouse models, resulting in reduced bone cancer pain and protection against bone loss by inhibiting the formation of osteoclasts and decreasing neuronal hyperactivity.

In these experiments, GPR37 activation led to lower firing rates in sensory neurons located in the dorsal root ganglion and spinal cord. The pain-relieving and bone-protective effects were not observed in mice lacking the Gpr37 gene, indicating the importance of this receptor in the process.

The studies collectively highlight several potential therapeutic approaches for managing bone cancer pain and tumor progression in preclinical settings. Each approach targets different biological pathways, offering multiple avenues for future research and development.

* This article is based on publicly available information at the time of writing.