HIV agent may prevent prostate Ca metastases

A receptor involved with HIV therapy also appears to be linked to prostate cancer metastases, according to recent research from Thomas Jefferson University, Philadelphia.

"Because this work shows we can dramatically reduce metastasis in pre-clinical models, and because the drug is already FDA approved for HIV treatment, we may be able to test soon whether this drug can block metastasis in patients with prostate cancer," said senior author Richard Pestell, MD, PhD, MBA, of the Sidney Kimmel Cancer Center at Thomas Jefferson University.

The work builds on previous research from Dr. Pestell's lab demonstrating that breast cancer cells that carried the CCR5 receptor on their surface were drawn to the lung, according to a Thomas Jefferson press release. Given that prostate cancer cells were attracted to the bone and brain, Dr. Pestell's team investigated whether CCR5 could play a role in prostate cancer metastases as well.

For the current study, which was published online in Cancer Research (Dec. 1, 2014), the authors developed a prostate cancer cell line, driven by an upregulated Src gene that regularly caused bone metastases in immune-competent mouse models.

Researchers analyzed the genes of the metastasized bone and brain tumors and found genes driving the cancer were also involved in the CCR5 signaling pathway. To investigate further, the authors administered the CCR5-blocking drug maraviroc (Selzentry) to the new prostate cancer mouse model. In comparison to control animals, maraviroc reduced the overall metastatic load by 60% in the bone, brain, and other organs.

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Finally, in order to determine whether a similar mechanism might be at play in human prostate cancer, the authors mined the genomic data of patients with prostate cancer and found that CCR5 was more highly expressed in prostate cancer tissue compared with normal tissue, and even more highly expressed in metastases compared with primary tumors.

The next steps are to develop clinical trials using CCR5 pathway activation as a companion diagnostic for the trial.

Dr. Pestell is founder of ProstaGene, LLC and owns patents related to prostate cancer cell lines and uses thereof.

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