Thursday April 10 2014
Scientists believe removing copper could kill cancer cells
"Copper can block growth of rare cancer," is the rather unclear headline in The Daily Telegraph. Researchers have found that a drug that reduces the amount of copper in the body may also be able to lessen the growth of some kinds of tumours.
These tumours – such as melanoma – have a mutation in the BRAF gene. BRAF helps create a protein that's vital for a biochemical pathway necessary for cell growth. Some cancers have a mutation in this gene, which means that the growth is unchecked and leads to a rapid spread of cancerous cells.
The researchers previously found that copper plays a role in the activation of this cell growth pathway. Trials of drugs that target this pathway have shown improved survival rates for people with multiple melanomas in previous research.
The researchers wanted to see if reducing copper levels could target the pathway in a similar manner. Using a range of experiments, they found that reducing the level of copper available to tumour cells decreased the growth of BRAF-mutated human cancer cells in the laboratory and BRAF-mutated tumours in mice.
They found that a drug used in humans as a treatment for Wilson's disease (a genetic disorder that results in a build-up of copper in the body) also had this effect. The researchers suggested that these drugs could be "repurposed" to treat BRAF-mutated human cancer.
The fact that these drugs are already used in humans could mean that they can be tested for their effects in cancer more quickly than a completely new drug. However, these trials are still needed before we know whether these drugs could provide a new approach to treating certain cancers.
Where did the story come from?
The study was carried out by researchers from Duke University Medical Center and the University of North Carolina in the US and the University of Oxford in the UK
It was funded by the National Institutes of Health, the Structural Genomics Consortium, an FP7 grant, the Halley Stewart Trust, the Edward Spiegel Fund of the Lymphoma Foundation, and donations made in memory of Linda Woolfenden.
The study was published in the peer reviewed medical journal, Nature.
In general, the media covered the story accurately, but the Mail Online reported that, "High levels of copper could mean an increase in deadly cancers", which is not what the study assessed or found.
What kind of research was this?
This was a laboratory study using mice and human tumour cells in the laboratory. The researchers previously found that copper plays a role in the activation of a particular cell growth pathway, which can lead to tumour formation if a gene called BRAF is mutated.
BRAF encodes a protein that activates a biochemical pathway of proteins necessary for cell growth. A particular mutation in this gene called BRAF-V600E has been found in some of the cells of cancers such as melanoma, colorectal cancer, thyroid cancer, and non-small-cell lung cancer (the most common type of lung cancer).
Drugs have been developed that inhibit BRAF-V600E or other proteins in this pathway, and trials are reported to have shown prolonged survival in people with metastatic (advanced) melanoma. However, tumours can become resistant to these drugs and researchers want to develop other ways of treating them.
The researchers aimed to see if restricting copper in tumours with BRAF mutations would reduce tumour cell growth in the lab and in mice, and improve the lifespan of the mice with these BRAF-mutated tumours.
What did the research involve?
The researchers used different approaches to reduce copper availability for tumour cells and tumours in the laboratory setting.
This included using mice genetically engineered to carry a mutation in genes, including BRAF, which can be triggered to result in lung cancers. They looked at what happened if these mice were also genetically engineered to lack a protein that transports copper into the cells.
Experiments were also performed in the laboratory and in mice using drugs that reduce copper levels in humans to see if these would reduce tumour growth.
Drugs that bind to copper, making it less available to be taken into cells, are already available to treat a condition called Wilson's disease, where people have too much copper in their bodies.
The researchers investigated the effect of one of these drugs on BRAF-mutated tumour cell growth in the laboratory and then in mice.
They also looked at the effect of stopping copper in the diet of the mice.
What were the basic results?
The researchers found that if the mice genetically engineered to develop BRAF-mutated lung tumours also carried mutations that reduced the ability to transport copper into their cells, this reduced the number of visible lung tumours. These mice also survived for 15% longer than mice with normal copper levels in their cells.
One of the copper-binding drugs was also able to reduce the growth of human BRAF-V600E melanoma cells in the laboratory. When mice were given the copper-binding drug, their BRAF-mutated tumours reduced in size.
Combining this with a copper-deficient diet improved the ability to reduce tumour growth, but the copper-deficient diet on its own did not have a significant effect.
The copper-binding drugs still worked, even when the tumours were resistant to BRAF-V600E inhibitors. The tumours started growing again when the treatment and diet were stopped.
How did the researchers interpret the results?
The researchers concluded that reducing copper availability in BRAF-mutated tumour cells decreases their ability to grow. They say that the copper-binding drugs, "which are generally safe and economical drugs that have been given daily for decades to manage [copper] levels in patients with Wilson disease", also decreased BRAF-mutated tumour growth in their experiments.
This suggests that these drugs warrant further assessment as potential treatments for BRAF mutation-positive cancers and cancers that have developed resistance to BRAF-V600E inhibitors.
This research has suggested that drugs already available that are designed to reduce the amount of copper in the body may be able to reduce the growth of tumours that have a mutation in the BRAF gene, such as melanoma.
The drugs reduced growth of BRAF-mutated tumours in mice and human cancer cells in the laboratory setting. Human clinical trials will be necessary to be certain that the drugs will have a beneficial effect in people with BRAF-mutated tumours before they could become widely used treatments for these types of cancers.
Although these drugs have already been shown to be a safe and effective treatment for Wilson's disease, the aim of that treatment is to get abnormally high copper levels down to a normal level.
Using the drugs as a cancer treatment could reduce the copper levels to below normal, and this could have side effects.
Copper deficiency causes blood abnormalities such as anaemia and an increased vulnerability to infection, as well as neurological problems such as nerve damage, so an appropriate dose and duration of treatment would need to be determined.
If human trials are successful, these drugs could provide a useful additional treatment option for hard-to-treat cancers such as melanoma.
Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.