Breast cancer is a difficult foe on its own, but patients often face an additional problem – degradation of their bones.
More than 70 percent of patients with metastatic breast cancer also have bone metastasis, which results in pain, fractures, nerve compression and other symptoms. Certain drugs can help stabilize patients’ bones, but only about half the time.
For Stephenson Cancer Center researcher Kelsi Andrade, PhD, that simply wasn’t acceptable. Andrade and her collaborators recently published a paper in the journal Science Translational Medicine that shows her significant headway toward making a difference in the lives of breast cancer patients.
“Breast cancer tends to spread to the bones first, and it literally results in holes in the skeleton,” she said. “Even for patients who are responding well to their cancer therapies, the bone destruction still causes ongoing problems.”
Andrade’s journal article details her research into the interaction between cancer cells and bone cells. Her laboratory was studying a specific signaling pathway called RON when she discovered that tumor cells express a ligand called MSP, or macrophage-stimulating protein. MSP is elevated in about 40 percent of breast cancer patients and leads to bone destruction. However, when she developed a research model targeting the tyrosine kinase receptor, which is essential to the RON pathway, bone destruction was almost completely blocked from occurring.
“The ligand being expressed by the tumor cells was interacting with the bone cells that expressed the receptor for that pathway,” she said. “That led to the tumor cells being very overactive. Normally, the body tries to balance bone destruction with bone building to maintain a healthy skeleton, but in this case the tumor cells were activated to levels where they started to destroy the bone. So it was very exciting to see that inhibiting the receptor blocked almost all bone destruction.”
Andrade then worked with a pharmaceutical company that develops RON inhibitors, and their work again showed in research models that bone destruction could be blocked to a significant degree.
The next step was testing the inhibitors in human cancer patients. Andrade partnered with a pharmaceutical company conducting a Phase 1 clinical trial, first testing patients’ blood samples to see if they had bone degradation. As expected, women in the trial had a higher level of bone degradation, even though they had cancers of various kinds. When the RON inhibitor was tested, the results were encouraging: 72 percent of women who had been treated for cancer for about a month saw a reduction in the markers that indicate bone destruction.
The next step is to test the inhibitors in a more specific trial of breast cancer patients.
“This is a less-studied area, which makes it more difficult to push things into the clinical arena,” Andrade said. “But our recent results were very encouraging, and we’re excited to see where it goes from here.”
As a researcher with the Stephenson Cancer Center, Andrade also interacts with her colleagues who are physicians, collaborating with them to design research investigations that address the specific needs of patients.
“Clinical input is very helpful,” she said. “Those interactions help me refocus my questions or my approach to a study in ways that push it toward making a difference in patients’ lives.”