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Researchers Identify Target of Metastasis in Triple-Negative Breast Cancer

Inhibition of the cat eye syndrome chromosome region candidate 2 (CECR2) gene pathway may prevent the development of metastatic disease in patients with triple-negative breast cancer, according to study results published in Science Translational Medicine.

The identification of this gene as an epigenetic regulator of metastasis for breast cancer suggests its potential utility as a treatment target for new therapy development, according to Qin Yan, PhD, from the Center for Epigenetics and Biomarkers at Yale School of Medicine.

To identify candidates for targeted breast cancer treatments, Yan and colleagues sought to determine the impact of tumor-associated macrophages on metastatic tumor development.

In particular, CECR2 emerged as an epigenetic and transcriptional regulator of metastasis in breast cancer. The expression of CECR2 was driven by the primary or metastatic status of the tumor, rather than estrogen receptor or HER2 status.

CECR2 acts as a driver of metastasis by activating the nuclear factor κB and EMT pathways, allowing cells to migrate to other parts of the body without being noticed by the host immune system.

Additionally, CECR2 may function as a target for breast cancer immunotherapy, allowing the inhibition of metastasis by blocking macrophage-driven immune suppression at metastatic sites and decreasing chromatin accessibility.

A CECR2 bromodomain inhibitor given to mice decreased macrophage polarization and severely limited the development of lung metastases.

“We are working on characterizing the mechanisms by which CECR2 modulates gene expression and tumor microenvironment using multiple cutting-edge technologies. In addition, we hope to develop small molecule inhibitors of CECR2 for clinical studies,” Yan and colleagues wrote.

Disclosures: No authors declared financial ties to drugmakers.

References:
https://www.science.org/doi/10.1126/scitranslmed.abf5473
https://www.yalecancercenter.org/news-article/yale-cancer-center-study-explores-new-path-to-treat-advanced-triple-negative-breast-cancer/

Images: Getty Images, Pixabay

By Cameron Kelsall, MD /alert Contributor

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