New skin cancer drugs show promise in lab tests

Behind the Headlines

Monday January 5 2015

Melanoma is a serious type of cancer that begins in the skin and can spread to other organs in the body

The drugs disrupt the messages that cancers spread

"New skin cancer drug set for clinical trials," The Guardian reports. In fact, two new compounds designed to treat malignant melanoma are due for trials after promising results in laboratory research.

Both are signalling inhibitors, which work by disrupting the messages a cancer uses to co-ordinate its growth. These have proven effective in the short to medium term, but it is common for the cancer to develop resistance to their effects.

This new research involved two new compounds, both part of a family called panRAF inhibitors, which work using a slightly different mechanism from existing signalling inhibitors.

The findings, involving mice and lab studies, were certainly encouraging, but we should not get ahead of ourselves. The research is barely out of the laboratory, which is the very first phase in the drug discovery timeline.

This means we have no idea whether these new drugs will be safe or effective when used on people.

Clinical trials will provide the answers over the coming years, although there are no guarantees that the drugs will be successful.

Small-scale clinical trials are the next stage in research, and the authors say this is planned.

 

Where did the story come from?

The study was carried out by researchers from the Cancer Research UK Manchester Institute, and the Institute of Cancer Research London.

It was funded by the Cancer Research UK Manchester Institute, Cancer Research UK, the Wellcome Trust and the Division of Cancer Therapeutics at the Institute of Cancer Research.

The study was published in the peer-reviewed science journal Cancer Cell as an open access article. This means that anyone can read the full article online for free.

Generally, The Guardian and the Mail Online reported the story accurately, though it wasn't made clear that the researchers were actually looking at two compounds, not a single drug.

The Mail also claims the research will lead to a "new pill". The study did not use a pill in the mice experiments – rather, the compounds were given orally as a liquid and an injection into a vein. 

It is too early to say with any assurance what form the drug would take if used in people.

The drug was for a resistant form of skin cancer, and these findings are at an early stage of research. 

 

What kind of research was this?

This was a laboratory study investigating biological compounds that have the potential to treat malignant melanoma with specific mutation in the BRAF gene. This is said to account for up to half of people with melanoma.

Melanoma is the most serious type of skin cancer, which can spread rapidly to lymph nodes and other organs in the body if not treated as soon as possible.

The most common sign of melanoma is the appearance of a new mole or a change in an existing mole. This can happen anywhere on the body, but the back, legs, arms and face are most commonly affected.

The study group say existing drug classes called BRAF and MEK inhibitors are initially effective when treating melanoma with the specific BRAF gene mutation.

However, in most people, the cancer comes back as the drugs stop working. In others, the drugs do not work very well to start with.

The team wanted to find new ways of treating this specific drug-resistant form of melanoma and began their investigations in the laboratory.

 

What did the research involve?

The research group designed and synthesised a variety of compounds as part of a drug discovery programme.

They focused their efforts using their understanding of the biological pathways involved in melanoma and, specifically, mechanisms by which current drugs stop working against the BRAF mutation.

The discovery programme led to two promising compounds, which underwent more in-depth biological and chemical experiments to work out exactly how they were working.

None of the experiments involved giving the newly developed drugs to people, although many involved testing the chemical on human cells cultured in the laboratory.

 

What were the basic results?

The discovery programme found two promising compounds. They are called pan-RAF inhibitors, named CCT196969 and CCT241161 respectively.

They were found to inhibit melanoma development through a different biological mechanism from previous drugs.

Because of this, it was hoped there may be less chance that resistance to these drugs will develop, as has happened in the past.

 

How did the researchers interpret the results?

The research team suggested the new chemicals they found, if developed into effective drugs, "could provide first-line treatment for BRAF and NRAS mutant melanomas and second-line treatment for patients who develop resistance".

In other words, these chemicals could potentially be developed into drugs to treat some melanomas in the first instance, and used as a second line of attack for others that have become resistant to existing drugs.

 

Conclusion

This laboratory study discovered two new chemicals, which show anti-cancer properties for melanoma with a specific gene mutation that can make it resistant to existing treatments.

The next stage for research is small-scale, phase I clinical trials to see whether these chemicals could one day be developed into drugs that could be available to treat patients. The authors say this is planned.

These types of trials generally assess whether the drug in development can be safely tolerated in people, and in what doses.

Only after they are deemed safe can further, larger trials be conducted to see whether the drugs work, or are cost-effective, in comparison to other treatments. These trials usually take many years.

There are no guarantees that any new drugs coming out of this research will turn out to be a winner, but there is hope.

Analysis by Bazian. Edited by NHS Choices. Follow Behind the Headlines on Twitter. Join the Healthy Evidence forum.

Analysis by Bazian

Edited by NHS Choices

Links to the headlines

New skin cancer drug set for clinical trials. The Guardian, January 2 2015

Revolutionary new PILL could treat skin cancer: Scientists discover drug could help patients resistant to standard treatments. Mail Online, January 3 2014

Links to the science

Girotti MR, Lopes F, Preece N, et al. Paradox-Breaking RAF Inhibitors that Also Target SRC Are Effective in Drug-Resistant BRAF Mutant Melanoma. Cancer Cell. Published online December 11 2014

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