Triple-negative breast cancer is considered to be more aggressive and has a poorer prognosis than other types of breast cancer, mainly because there are fewer targeted medicines that treat triple-negative breast cancer. Studies have shown that triple-negative breast cancer is more likely to spread beyond the breast and more likely to recur after treatment. A new study by researchers at Yale Cancer Center shows inhibition of the CECR2 gene prevents triple-negative breast cancer from advancing or metastasizing in mice.

The findings are published in the journal Science Translational Medicine in a paper titled, “CECR2 drives breast cancer metastasis by promoting NF-κB signaling and macrophage-mediated immune suppression.”

“Metastasis is the major cause of cancer-related deaths due to the lack of effective therapies,” the researchers wrote. “Emerging evidence suggests that certain epigenetic and transcriptional regulators drive cancer metastasis and could be targeted for metastasis treatment. To identify epigenetic regulators of breast cancer metastasis, we profiled the transcriptomes of matched pairs of primary breast tumors and metastases from human patients.”

“These study results are very encouraging as there are few effective treatments for triple-negative breast cancer once it has metastasized,” explained senior study author Qin Yan, PhD, associate professor of pathology and director of the Center for Epigenetics and Biomarkers in the department of pathology at Yale School of Medicine, co-leader of the genomics, genetics, and epigenetics research program, and scientific co-director of the Center for Breast Cancer of Yale Cancer Center. “We are constantly searching for new effective therapeutic strategies to help patients with this potentially deadly disease.”

The researchers profiled 13 pairs of primary and metastatic breast tumor samples from patients with breast cancer. They identified a therapeutic target, a gene called cat eye syndrome chromosome region candidate 2 (CECR2), that increased expression in the tumors that have spread to distant organs.

The research team discovered that CECR2 allowed the breast cancer cells to migrate and invade adjacent tissues and evade surveillance by the host immune system.

“The acetyl-lysine reader, CECR2, was the top up-regulated epigenetic regulator in metastases associated with an increased abundance of M2 macrophages and worse metastasis-free survival,” the researchers wrote. “CECR2 was required for breast cancer metastasis in multiple mouse models, with more profound effect in the immunocompetent setting.”

“We will continue to study these important findings,” added Yan. “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.”

The discovery is an early step in finding new therapeutics for triple-negative breast cancer.

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