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Research in Review

Bone Model Examines Treatment Effectiveness for Breast Cancer Metastases

A bone metastasis model has been created that simulates interactions between metastatic breast cancer cells and bone cells to determine effectiveness of different treatments, published in Nature Communications (published online April 21, 2017; doi:10.1038/ncomms15045).

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Many patients with breast cancer are able to eliminate their primary tumors through standard means. However, occurrence of tumor metastasis is not as easily treatable. Metastases tend to respond differently than primary tumors to standard treatment because of their respective microenvironments; metastases disseminate most frequently to bone cells. There has yet to be an effective experimental platform to study metastatic tumors in their new microenvironments.

Xiang Zhang, PhD, associate professor of molecular and cellular biology, Lester and Sue Smith Breast Center, Baylor University (Texas), and colleagues developed a bone metastases model, called bone-in-culture array, that allows for testing of many different and simultaneous drug responses to observe the therapy that can best act on metastatic cancer cells while minimizing effects on the bone. Researchers fragmented mouse bones that contained breast cancer cells. They determined that the bone-in-culture maintains the characteristics of bone metastasis in living animal models. Additionally, they determined that cancer cells maintain gene expression profile, growth patterns, and response to therapies.

Researchers found that the drug danusertib – an inhibitor of the Aurora kinase family – inhibits bone metastasis. In contrast, they found that certain histone methyltransferase inhibitors stimulate metastatic growth of cancer cells in the bone. Bone-in-culture was also found to aid in investigating mechanisms involved in bone colonization by cancer cells.

"We think that this new system has the potential to be applied not only to breast cancer but to other cancers that also metastasize to the bone," Dr Zhang said in a press release (April 21, 2017). "This technique can be scaled up to larger sample sizes, which would help accelerate the process of discovering metastatic cancer treatments. We have already found a few interesting drugs. We will keep looking for more and focus on those that are most promising."

The model is expected to develop into a standardized system for identifying specific drugs to better treat metastatic cancer. – Zachary Bessette

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