Treatments that ‘revolutionized cancer therapy’ may increase risk for bone damage
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To help individuals who undergo cancer treatment lead healthier lives, Stacyann Bailey, PhD, has one overarching professional mission — to prevent bones from breaking.
NCI has awarded a 2-year grant to Bailey, an assistant professor of biomedical engineering of the University of Massachusetts Amherst, to conduct research into the association between immune checkpoint inhibitors and bone damage.
Bailey will use the $392,617 grant to assess the effects of immune checkpoint inhibitors on bone damage and fracture in patients whose primary cancer has metastasized to the bone.
“Immune checkpoint inhibitors have revolutionized cancer therapy in the past decade and are now the preferred treatment for several advanced tumors,” Bailey told Healio. “However, studies have found that there are some skeletal adverse effects, which can include the formation of new bone lesions, bone loss and vertebral fractures. We don’t know why because we don’t have enough data to tease this out.”
Bailey spoke with Healio about the timeline of her upcoming research and discussed how her potential findings could inform treatment decisions in patients with bone metastases.
Healio: How common are fractures in patients with bone metastases?
Bailey: Generally, there is a high risk — up to 50% of patients with bone metastases will develop a fracture. The cancers in which bone metastases are most common include primary breast, prostate, lung, kidney and esophageal cancers.
Healio: Beyond fracture risk, how else can bone metastases impact patient quality of life?
Bailey: This depends on the skeletal site of the metastases. If they are in the spine, for example, the patient may have spinal cord compression or neurologic defects. Additionally, patients with bone metastases have hypercalcemia, and calcium is important to the strength and mechanical integrity of the bone. The result is that these patients will have decreased quality of life and increased morbidity because they are less able to perform certain daily activities. Their bones are fragile, which can make tasks like bending over to tie shoelaces, going up and down stairs, or going from sitting to standing quite problematic. Patients also experience pain when cancer has metastasized to the bone.
Healio: What is currently known about the effect of immune checkpoint inhibitors on bones?
Bailey: Although we are aware of skeletal adverse effects associated with immune checkpoint inhibitors, these effects have not been a major area of focus. Often with immune checkpoint inhibitors, we’re looking for adverse events related to inflammation, or effects like skin rashes, diarrhea or fever. Skeletal effects are not at the forefront.
Healio: What specific research will you conduct on the association between immune checkpoint inhibitors and bone damage/fracture risk?
Bailey: Through an animal model, we hope to understand the mechanism behind increased bone loss and fracture risk seen in patients receiving checkpoint inhibitors. We will study this in a controlled setting and evaluate different dosages and different types of checkpoint inhibitors. We will also explore sexual dimorphism and cancer type variations. We plan to analyze heterogeneity within cancer types, and we will consider the hormonal component of some of these cancer subtypes and their treatments.
This approach will also allow us to test the effects of checkpoint inhibitors and anti-osteoporotic drugs in hopes of achieving synergistic anticancer efficacy while mitigating bone loss and fragility. Currently, there is a dearth of information on combination therapies in clinical trials, and knowledge is also limited on the effects of monotherapy with immune checkpoint inhibitors on bone-related outcomes.
We also hope to obtain human bone samples of metastatic cancer from individuals who graciously donated their tissues to research. We plan to analyze these samples to identify unique biomarkers that could predict lesion heterogeneities. These biomarkers could enable us to develop a predictive model of fragility. We aim to explore more of a personalized medicine approach, as well as risk-adapted selection for ongoing therapies and future therapies.
Healio: What is your timeline for conducting this research?
Bailey: Our animal protocol was just approved. We’ve simultaneously been procuring human tissue through our clinical partners. We also have students and research technicians who can drive the different parts of this project at the same time.
Healio: What do you hope will be the implications of these analyses?
Bailey: We want to make a positive impact in terms of using biomarkers to guide individualized therapy. We want to promote patient awareness and clinician awareness, and we want to help them make the best decision to help the patient have a better quality of life. Perhaps we will be able to look into treatment guidelines for certain tumor types, clinical characteristics or pathologic characteristics. Our lab is a basic science lab, but we are poised to share our findings so that those who are more adept and equipped can make those changes.
Healio: Is there anything else you’d like to mention?
Bailey: Immune checkpoint inhibitors and immunotherapy in general have changed how we treat patients — these are the treatments of choice for many cancers. They’re very good at reducing tumor burden and extending overall survival. We are certainly not criticizing these therapies. We just want to determine how we can mitigate immune-related effects in patients receiving them. Our goal is to make sure that patients lead a healthy life without harm.
Reference:
- Bad to the bone: UMass Amherst engineer aims to prevent fracture in cancer patients (press release). Available at: https://www.umass.edu/news/article/bad-bone-umass-amherst-engineer-aims-prevent-fractures-cancer-patients. Posted Jan. 22, 2024. Accessed Feb. 19, 2024.
For more information:
Stacyann Bailey, PhD, can be reached at University of Massachusetts Amherst, Life Science Laboratories, 240 Thatcher Road, Amherst, MA 01003; email: stacyann.bailey@umass.edu.
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