HIV drug may slow the spread of prostate cancer

Monday December 1 2014

“A drug used to treat HIV infection can slow the spread of prostate cancer, research has shown,” The Independent reports.

The news centres on the drug maraviroc (Celsentri), which researchers have found may slow the spread of prostate cancer into the bone and brain in early tests in mice.

Each man’s prostate cancer can progress in different ways. Many cases grow slowly, and the cancer remains within the prostate. A minority of cases are highly aggressive and can spread into other areas of the body, such as bones and the brain – a process known as metastasis.

In this research, scientists found a way to prompt mouse prostate cells to take on the characteristics of metastatic cancer cells, and then studied what proteins played a role in this change.

A protein called CCR5 was found to be implicated. Luckily maraviroc, a drug licensed for treating people with HIV, is already known to inhibit this protein. Giving maraviroc to mice that had been injected with the prostate cancer-like cells reduced the spread of the cancer to brain and bone by more than 60%.

This is still very early-stage research, and we will need to see the results of human trials before we know whether this drug is effective for preventing or treating prostate cancer metastases in humans.

Where did the story come from?

The study was carried out by researchers from Thomas Jefferson University in the US and other universities in the US, Italy and Mexico. It was funded by the US National Institutes of Health, the Dr. Ralph and Marian C. Falk Medical Research Trust, the Margaret Q. Landenberger Research Foundation, the Pennsylvania Department of Health, The National Autonomous University of Mexico and Thomas Jefferson University.

One of the authors is the founder of a company called ProstaGene, LLC and AAA Phoenix, Inc., and owns patents relating to prostate cancer cell lines and uses for these.

The study was published in the peer-reviewed medical journal Cancer Research on an open access basis, so it's free to read online.

The Independent covered this study accurately, if briefly, stating that the research was at an early stage and carried out on mice. The Daily Express also provides an accurate summary of the study, along with some useful background information about prostate cancer.

What kind of research was this?

This was animal research looking at how prostate cancer cells spread (metastasise) to bone, and how this might be stopped.

When prostate cancer spreads in the body, it often spreads to bone. Researchers would like to know why this is and how to stop it. None of the existing mouse models of prostate cancer reliably develop bone metastases, and this makes it difficult to study. The researchers wanted to develop a mouse model of prostate cancer, which would develop bone metastases, and use it to study this condition.

Animal studies are often used to get a better understanding of the biology of human disease and how it might be treated. The biology of animals such as mice has a lot of similarities to humans, but there are also differences. This means that results seen in mice won’t always be seen in humans, so human studies are needed to confirm initial findings in mice.

What did the research involve?

The researchers obtained cells from mouse prostate tissue and used genetic engineering to get them to produce an abnormally active form of a protein called Src, which encourages cells to become cancerous. They then looked at whether the cells divided and moved more in the lab, allowing them to “invade” a gel substance that resembles body tissue. These characteristics indicate whether the cells are behaving more like cancer cells spreading in the body. They also looked at what happened if they injected these cells under the skin or into the bloodstream of mice.

The researchers then compared which genes were active in normal mouse prostate cells, in the genetically engineered prostate cancer-like cells grown in the lab and those injected into the mice. Genes that are more active in the cancer-like cells could be contributing to their growth and spread. After this, the researchers looked at whether any of these genes were also more active in human prostate cancer tissue, using a bank of existing data on gene activity in human tissues.

Once they identified a gene that could be playing a role in prostate cancer, they carried out a range of experiments to further look at its effects. These included tests looking at whether stopping the protein produced by this gene from working may stop the spread of the genetically engineered prostate cancer tumours in the mice.

What were the basic results?

Prostate cells producing the abnormally active Src protein divided and moved more, and were more invasive in the lab. They grew into tumours if injected under the skin of mice, and if injected into the bloodstream, they spread to various organs, including the bone and brain. The tumours in the bone still had the appearance of prostate cancer tissue.

Genes playing a part in a particular pathway called the CCR5 signalling pathway were more active in these prostate cancer-like cells than in normal mouse prostate cells. The CCR5 gene was also found to be more active in human prostate cancer, particularly metastatic cancers. This and previous research suggests this gene could be contributing to the spread of the prostate cancer cells.

An HIV drug called maraviroc stops the protein produced by the CCR5 gene from working as effectively, so the researchers tested whether it could prevent the cells from spreading. They found maraviroc stopped the mouse prostate cancer-like cells from being invasive in the lab.

The researchers also found that giving maraviroc to mice injected with mouse prostate cancer-like cells also reduced metastases by more than 60%.

How did the researchers interpret the results?

The researchers concluded that they had developed a new mouse model of human prostate cancer, which may be a useful addition to the existing models of this disease. The protein CCR5 appears to be more active in metastatic prostate cancer cells. The spread of these cells in mice is reduced by the oral CCR5 inhibiting drug maraviroc, which is already approved as a treatment for HIV. The results suggest that clinical trials might be warranted for maraviroc or similar CCR5 inhibiting drugs in men with prostate cancers found to have high levels of CCR5 activity.

Conclusion

This animal research has identified the protein CCR5 as potentially playing a role in how prostate cancer cells spread (metastasise) through the body. The study has also shown that a drug already on the market for treating HIV, called maraviroc (brand name "Celsentri") can reduce prostate cancer-like metastases in mice.

As the drug maraviroc has already obtained a license for HIV use, there is already evidence suggesting that it is safe enough for use in humans. This could mean that clinical trials of this drug for prostate cancer could take less time to happen than if this was a new chemical compound whose safety had not been previously tested in humans.

However, it’s worth bearing in mind that this is still very early-stage research. Researchers are likely to want to carry out more studies on human prostate cancer tissue and cells in the lab, and in animals, to confirm that CCR5 is playing a role in the spread of prostate cancer. We will need to see what the results of human trials are before we know whether this drug is effective for preventing or treating prostate cancer metastases in humans.

Analysis by Bazian
Edited by NHS Choices