Researchers identify protein that spreads cancer

Tuesday July 14 2015

Researchers found the DNA-PKcs molecules helped spread cancer

“Scientists have found a way of preventing the spread of cancer from the site of the original tumour,” The Independent reports. Targeting proteins called DNA-PKcs could prevent cancer cells moving to other parts of the body. This is known as metastatic cancer and is often fatal.

The research involved mice as well as tissue samples from more than 200 prostate cancer patients. Researchers found mice treated with an inhibitor to block DNA-PKcs had reduced cancer spread compared with mice that were not treated.

Patients whose prostate cancer tissue samples showed higher DNA-PKcs levels were more likely to have had cancer progression (metastasis). As yet we do not know if a DNA-PKcs inhibitor would have the same outcome in humans as it did in mice.

This research furthers our knowledge about the biology of cancer progression and has identified another possible way to tackle the spread of cancer. Further investigation in humans would be required to confirm whether these findings are of use for improving outcomes for prostate cancer patients.  

Where did the story come from?

The study was carried out by researchers from Thomas Jefferson University, the University of Michigan, Cleveland Clinic, the University of California, Los Angeles (UCLA), the Mayo Clinic, Columbia University Medical Centre, and GenomeDx Biosciences.

It was funded by the Prostate Cancer Foundation (PCF), PCF/Movember and Evans Foundation, PA CURE, the US Department of Defense, UCLA, the National Cancer Institute, and the National Institutes of Health.

The study was published in the peer-reviewed journal Cancer Cell.

This research has been reported in the media as a breakthrough – the Daily Express goes as far as talking about a possible “cure”. However, while certainly promising, the research is at an early stage. Crucially, we do not know whether these findings will result in new treatments in humans.  

What kind of research was this?

This laboratory and animal study in mice looked at whether the protein DNA-PKcs is linked to cancer progression. This type of animal study is used to understand the biology of human disease better.

While there are a lot of similarities in the biology of different species, there are some key differences. This means that while results do give an indication of what is likely to happen in humans, we cannot be certain that any findings would be exactly the same.

Researchers looked at some prostate cancer tissue samples to see if their findings looked like they might apply to people, but the human research is at an early stage. 

What did the research involve?

The researchers first studied DNA-PKcs in cells in the lab to look at what it does in the cell. It was believed to aid the spread of cancer cells.

They then used mice injected with human prostate cancer cells to investigate whether it is possible to stop cancer spread by targeting the DNA-PKcs protein.

Mice were either treated with an inhibitor that blocks the DNA-PKcs protein or an inactive control treatment. The size of their tumours was monitored by live imaging.

After 31 days three mice were selected from the control arm and switched to receive the DNA-PKcs inhibitor to investigate the impact. Three mice were also selected from the protein inhibitor group and stopped receiving this treatment.

The researchers went on to analyse cancer tissue samples from 232 patients with prostate cancer, and measured the amount of DNA-PKcs the cells contained. The researchers looked at how their DNA-PKcs levels related to their outcomes. 

What were the basic results?

The laboratory tests showed the DNA-PKcs protein was involved in controlling the activity of genes cancer cells need to move and spread. The researchers also found blocking DNA-PKcs reduced the spread of cancer in mice.

Mice who crossed over from the control arm to the protein inhibitor did not show a reduction in tumour size. This implies the DNA-PKcs inhibitor blocked the spread of cancer rather than suppressing tumour growth.

When mice stopped receiving the DNA-PKcs inhibitor, their cancer spread. Mice who stayed on the DNA-PKcs inhibitor and did not cross over were found to have less cancer spread than those who stayed in the control arm.

The patient samples showed men with higher DNA-PKcs levels were more likely to have had prostate cancer progression and to have died. 

How did the researchers interpret the results?

The researchers concluded they have identified DNA-PKcs as a protein that drives prostate cancer progression and spread.

Higher levels of DNA-PKcs in prostate cancer tissue were an independent predictor of metastasis, recurrence and poor survival. Researchers hope this discovery will pave the way for new drug treatments. 

Conclusion

This lab study in mice found a protein called DNA-PKcs is involved in the spread of cancer cells, and assessed whether it is possible to stop this spread by targeting the protein.

It demonstrated that mice with human prostate cancer cells treated with an inhibitor to block the protein had reduced cancer spread compared with those who were not treated.

Analysis of patient prostate cancer samples showed higher DNA-PKcs levels were linked to a greater risk of cancer progression. This suggests the protein may be playing a similar role in humans, and researchers will want to go on to see if DNA-PKcs inhibitors could be used as a new treatment to stop the spread of cancer.

This protein is involved in the spread of cancer but does not appear to be involved in cancer growth, so any new drugs blocking it would also need to be used alongside other drugs. It’s also not yet clear whether the findings only apply to prostate cancer cells.

While this research seems to show promise, the findings on the DNA-PKcs inhibitors were in mice and therefore may not be applicable to humans. Headlines reporting this as a cancer “breakthrough” should be taken with caution.

Researchers will need to determine whether these inhibitors seem safe and effective enough in animals before they could be tested in humans. Once this is done, a randomised trial in humans would be required before we know its effects.