New insight into drug resistance in metastatic melanoma

June 3, 2014 by Alison Barbuti

(Medical Xpress)—A study by scientists in Manchester has shown how melanoma drugs can cause the cancer to progress once a patient has stopped responding to treatment.

Their findings suggest that using a combination of targeted therapies may be a more effective approach in the clinic.

Melanoma is a form of that develops from – the pigment-producing cells in skin. Advanced metastatic – where the cancer has spread throughout the body – is associated with poor survival, so new treatments are urgently needed.

In about 50% of melanoma cases, the tumour contains a mutation in a gene known as BRAF. Drugs that target BRAF – such as vemurafenib – have increased survival in patients with this mutation. However, many of these patients go on to develop resistance to treatment and their disease returns.

Now researchers from the Cancer Research UK Manchester Institute at The University of Manchester – part of the Manchester Cancer Research Centre – have explored what happens in melanoma cells following inhibition of BRAF.

Professor Richard Marais, who led the research, said: "BRAF inhibitors have improved survival for patients with . Unfortunately, eventual drug resistance is preventing long-term cure in most of these patients. We wanted to understand how these drugs might induce unwanted effects in melanoma cells – particularly in cells which also have a mutation in the RAS gene."

The group found that blocking BRAF activity, either using drugs or by altering a cell's genes, led to the RAS-mutated melanoma cells changing shape and becoming more invasive. These changes in behaviour would lead to metastatic spread of the disease throughout the body. Their study, published recently in the journal Science Signaling, showed that the BRAF inhibitors re-activated certain pathways within cells leading to melanoma cells becoming resistant to therapy.

"We found that we could counteract this behaviour by adding a second drug to the BRAF inhibitor – one that targets MEK. It looks like our study further supports the combined use of both BRAF and MEK inhibitors in melanoma patients," added Professor Marais.

Explore further: Scientists find new way to combat drug resistance in skin cancer

Related Stories

Recommended for you

Ancient stress response provides clues to cancer resistance

April 25, 2017

Cancer is often able to craftily outwit the best techniques modern medicine has developed to treat it. In an attempt to understand and combat cancer's vaunted prowess, an unusual collaboration between physicists and a leading ...

Studying a catalyst for blood cancers

April 25, 2017

Imagine this scenario on a highway: A driver starts to make a sudden lane change but realizes his mistake and quickly veers back, too late. Other motorists have already reacted and, in some cases, collide. Meanwhile, the ...

Savior of T-cells may be enemy of liver immune cells

April 24, 2017

Researchers at Houston Methodist demonstrated that a surface protein called OX40, responsible for keeping one type of immune system cell alive, can trigger the death of liver immune cells, in turn starting a chain reaction ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.