New 'Bone-in Culture Array' Tests Therapies for Breast Cancer Metastasis
A new laboratory technique developed by researchers at Baylor College of Medicine and other institutions can rapidly test the effectiveness of treatments for life-threatening breast cancer metastases in bone. Findings of this research were published by Wang et al in Nature Communications.
“For a number of patients [with breast cancer], the problem is metastasis after the primary tumor has been eliminated,” said corresponding author Xiang Zhang, PhD, Associate Professor of Molecular and Cellular Biology at the Lester and Sue Smith Breast Center at Baylor. “Metastases, however, tend to respond differently than the primary tumor to the treatment, in part due to residing in a different organ with a different microenvironment.” Until now, there has not been an effective experimental platform to study metastatic tumors in their new microenvironment.
“We have created an experimental system in which we can mimic the interactions between cancer cells and bone cells, as bone is the place where breast cancer and many other cancers disseminate most frequently,” said Dr. Zhang, who also is a McNair Scholar at Baylor. “We have developed a system that allows us to test many different drug responses simultaneously to discover the therapy that can selectively act on metastatic cancer cells and minimize the effect on the bone.”
Bone-in Culture Array
To mimic the interactions between metastatic breast cancer cells and bone cells in a living system in the lab, Dr. Zhang and his colleagues developed a bone metastasis model, called a “bone-in culture array,” by fragmenting mouse bones that already contain breast cancer cells. The scientists determined that the bone-in culture maintains the microenvironmental characteristics of bone metastasis in living animal models, and the cancer cells maintain the gene-expression profile, growth pattern, and response to therapies.
Using the bone-in model, the researchers determined that the drug danusertib, an investigational pan-aurora kinase inhibitor, preferentially inhibits bone metastasis. They also found that other drugs stimulate the growth of slow-growing cancer cells in the bone. In addition to determining the effect of drugs in the growth of metastasis in bone, the bone-in culture can be used to investigate 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. “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 scientists expect to develop this platform into a standardized system that can be used in the clinic to find specific drugs that can better treat metastatic cancer.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
