‘Skin cancer drug resistance may be solved’

28 May 2014

The rapid resistance to a drug designed to treated a type of advanced melanoma - the deadliest form of skin cancer - could be prevented by blocking a particular family of proteins, according to new research published in the journal Nature Communications.

Advanced melanoma skin cancer spreads across the body, most commonly metastasising to the lungs, liver, bones and brain. Treatment options in later stages of the disease are limited to medicines that slow the escalation of the disease and reduce symptoms, such as chemotherapy.

According to the NHS, the condition is relatively rare, but is become increasingly common, with 13,000 new cases being diagnosed every year in the UK. It generally develops in people aged between 15 and 34 and is responsible for the most skin cancer deaths. Unfortunately, over 2,000 people die each year due to the condition. 

The new research - undertaken by scientists at the University of Manchester - suggests the MLK family for four enzymes reverse the tumour shrinking effects of vemurafenib, which is designed to specifically treat advanced melanoma.

Almost half of metastatic melanomas are caused by a defect in the cell-growth gene BRAF, causing the signal telling cells to multiply and be permanently activated. Vemurafenib blocks the faulty gene to stop the spread of the disease, but the cancerous cells usually find a way to turn it back on, thereby cancelling the effect of the drug.

After around six months, most metastatic melanoma patients stop responding to the drug which leads to a relapse of the disease.

However, there may be hope as the new research reveals that MLK enzymes are responsible for reactivating the BRAF pathway, even when vemurafenib is present in the body. By blocking these enzymes, researchers hope to inhibit cancer cells’ resistance to the drug so it can continue to stop the spread of the condition. 

In addition, the findings also demonstrated that some some melanoma patients have additional gene mutations that switch MLK enzymes on, causing them to develop a resistance to vemurafenib more quickly than others.

Dr John Brognard, lead author of the study, said: “This exciting research reveals that melanoma cells have enzymes acting like a manual override switch to regenerate growth signals – even after vemurafenib has switched them off.

“Additionally, this family of enzymes are turned on in metastatic melanomas that are not caused by BRAF, suggesting they may serve as a new target in metastatic melanomas for which there are limited treatment options.”

He said there were already experimental drugs available that are able to block these particular enzymes in laboratory conditions. This research, in his opinion, paves the way for developmental medicines to overcome vemurafenib resistance in melanoma patients.

Professor Nic Jones, Cancer Research UK’s chief scientist, added that the findings open new routes to treat pancreatic cancer. He thanked the public for their generosity, which has helped to fund studies into BRAF gene, leading scientists to discover it is behind half of all melanomas. 

He continued: “Rates of melanoma in Britain are now five times higher than in the mid-1970s, but survival rates have also improved, with more than eight in ten  surviving for more than ten years. We hope this latest research will lead to new treatments enabling even more people to beat this disease. Melanoma research is a key priority for the Manchester Cancer Research Centre.”

Posted by Jeanette Royston


Health News is provided by Adfero in collaboration with Spire Healthcare. Please note that all copy above is ©Adfero Ltd. and does not reflect views or opinions of Spire Healthcare unless explicitly stated. Additional comments on the page from individual Spire consultants do not necessarily reflect the views or opinions of other consultants or Spire Healthcare.

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