CCR5 antagonists have been in the mix now for years as a treatment for HIV. But scientists at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia produced promising results using the drugs to prevent aggressive breast cancers from reaching metastasis.
Details of their preclinical study are published in Cancer Research. Specifically, CCR5 antagonists target the HIV receptor CCR5--crucial for the virus as a pathway to enter and infect host cells, the researchers note. Their discovery builds on their finding that CCR5 is also expressed in breast cancer cells as well as immune system inflammatory cells, and they additionally appear to help regulate the spread of cancer to other tissue.
For their test they used CCR5 antagonists Maraviroc (marketed by Pfizer as Selzentry, as a first-line AIDS drug), and Vicriviroc, (a drug that failed for Merck as an HIV treatment). In HIV, they are supposed to work by hitting the CCR5 co-receptor of the chemokine CCL5. For breast cancer cells, both drugs also generated some benefit, preventing the cells from migrating and spreading.
"Our team showed that the CCR5/CCL5 axis plays a key role in invasiveness," Richard Pestell, director of the Kimmel Cancer Center and a senior study author, said in a statement. "A CCR5 antagonist can slow down the invasion of basal breast cancer cells." Pestell added that he sees the drug as possibly working as an added therapy to reduce the risk of metastasis with the basal breast cancer subtype.
The group performed their tests on 2,254 patient breast cancer samples and also in mice. While the cancer testing in humans could be years away, results were promising in mice, on which scientists tracked metastases of breast cancer cells into lungs and other tissue. Mice treated with the drug saw their pulmonary metastases drop in size and number 90%, compared with cancer-stricken mice that didn't receive treatment.
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Selzentry - 2007 FDA approvals
Vicriviroc - Top 10 Phase III Failures