For some patients whose cancer has spread to their bones, the ensuing treatment can be more physically damaging than the original disease, leading to increased bone loss and fracture. Stacyann Bailey, assistant professor of biomedical engineering at the University of Massachusetts Amherst, has received a two-year grant from the National Cancer Institute to study the complex relationship between drugs used to treat metastatic cancer and the development of bone damage.
While there is much attention on early detection and diagnosis, our patients are not dying from primary cancer. They're really dying from metastasis, whether it's to the lung, the brain, or the bone, which is the subject of my research. Breast cancer, prostate cancer, lung cancer, kidney cancer-;those are the top primary cancer types that eventually break off from that primary site and make its way into the bone."
Stacyann Bailey, assistant professor of biomedical engineering, University of Massachusetts Amherst
Bailey's new $392,617 grant will allow her to focus on this bone damage in late-stage cancer patients and determine whether immune checkpoint inhibitor cancer treatments can decimate bone.
"When you give a patient an immune checkpoint inhibitor, it does a really good job at killing the tumor cells, which is what we want," she says. "However, for some unknown reason, which is a goal of the grant, it seems like activating the immune cells-;or overactivating the immune cells-;now has bad effects on the bone."
Bailey suspects it's because immune cells have their own relationship with bone cells. "People don't understand how central your bone is to your immune system," she says. "Your immune cells are housed there. Immune cells regulate bone formation as well as bone resorption [the process by which the body breaks down bone to release stored minerals]. I can think of every other system that we can link bone to-;reproductive, endocrine, urinary, digestive."
Fracture is already a significant concern for patients with metastatic bone disease. "When the cancer cells go to bone, there's already bone loss, there's already risk of fracture," Bailey explains. Up to 50% of patients with metastatic bone disease develop fractures depending on the primary tumor type and bone site, and immune checkpoint inhibitor therapy appears to compound the issue.
"My long-term, big picture will be: how can we prevent fractures from happening?" she says. "Because when we do that, then patients can live longer and they can have a better quality of life," like avoiding multiple surgeries and prolonged bed rest while managing other comorbidities, such as diabetes, osteoporosis and Alzheimer's disease, that also independently affect bone health, she adds.
This grant will allow Bailey to explore several facets of this condition. The first is determining if the immune checkpoint inhibitors are to blame for the bone damage, because that mechanism is poorly understood: "If it is true that they are causing these harmful effects, then can we mitigate that? Can we use a second therapy to slow down that progression?" Second, she hopes that they can use protein biomarkers native to the tissues to create a model that will predict-;and ultimately prevent-;fractures from happening.
She names several possible outcomes of her work, including patient awareness, improved treatment guidelines, drug development based on targeting one of these biomarkers and even manufacturing material with the same proteins to help to repair and regenerate the tissue.
"Those are the broad categories of where my work would fit in, but bottom line, I want to stop bones from breaking," she says.
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