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Precision medicine approaches and treatments for breast cancer, published by Blumberg Institute scientists

 Drug used to treat HIV shows potential in treating triple-negative breast cancer in animal study.

Doylestown, June 4, 2021 – A team of researchers at the Baruch S. Blumberg Institute is producing new insights into the treatment of breast cancer, particularly triple-negative breast cancer. Unlike Her2+ or ER+ breast cancer, triple negative breast cancer is the worst prognosis breast cancer type, without therapies that can target a specific molecular genetic weakness in the cancer.

The study was led by Richard G. Pestell, M.D., Ph.D., distinguished professor of translational medical research at the Blumberg Institute. Dr. Pestell’s laboratory had previously analyzed more than 2,200 breast cancers and found a potential genetic target in triple negative breast cancer called CCR5. In the latest study they tested this target using a specific therapy.

Their latest study, published in Breast Cancer Research (Jan. 23), shows that a humanized monoclonal antibody targeting CCR5 called leronlimab, which has a strong safety profile in clinical trials for HIV, was effective in blocking the metastatic spread of human triple negative breast cancer in mice. Leronlimab also reduced the progression of many of the established metastasis.

“Triple negative breast cancer often has a poor prognosis with limited treatment options, typically surgery, chemotherapy and radiation, with associated significant side-effects reducing the patients’ quality of life,” Dr. Pestell said. “Several recent clinical trials are now targeting CCR5 in cancer. The effectiveness of leronlimab in preventing metastasis and reducing the size of the metastases provides further support for carefully controlled clinical trials.”  

In related precision medicine studies of breast cancer Pestell’s laboratory revealed in Cell Reports (Sept. 15, 2020) that cyclin D1, thought to be a nuclear oncogene has an additional function in the cell membrane. Cyclin D1 is overexpressed in a large proportion of human breast cancers, but targeted therapies help only a subset of patient. The Cell Reports studies show that cyclin D1 which resides outside the nucleus in a membrane pool, activates another pathway to induce tumor growth called Akt. Their publication in the journal Oncogenesis (Sept. 18), showed this renegade pool of membrane cyclin D1 promotes tumor invasiveness. Together these studies suggest an opportunity to target membrane cyclin D1 with Akt inhibitors.

The Blumberg Institute team had found earlier in the year that cyclin D1 also controls a cluster of non-coding miRNA that are secreted from the breast cancer cell and activate oncogenic immune signals (Clinical Science, April 9), “Cyclin D1 promotes secretion of pro-oncogenic immuno-miRNAs and piRNAs). “The ability of cyclin D1 to restrain the body’s normal anti-tumor immune system may be one more mechanism by which these breast cancers evade current therapies.”

Dr. Pestell added, “A detailed understanding of the molecular events by which cyclin D1 promotes tumorigenesis is essential to provide more effective and longer lasting remissions for breast cancer survivors.”

About the Baruch S. Blumberg Institute: An independent nonprofit research organization, the Institute was launched in 2003 by the Hepatitis B Foundation to advance its research mission. Today, the Institute is one of the nation’s leading centers for translational research, particularly for hepatitis B and liver cancer. The Institute supports drug discovery, biomarker discovery and translational biotechnology around common research themes such as chronic hepatitis, liver disease and liver cancer in an environment conducive to interaction, collaboration and focus. The Institute is located in the Pennsylvania Biotechnology Center, which it manages, near Doylestown, Pa. For more, go to www.blumberginstitute.org and follow us on Twitter @BlumbergInstit1. To donate, contact Jean Holmes at 215-489-4900 or jean.holmes@hepb.org.