New way to combat skin cancer drug resistance discovered

A new discovery has been made that could help patients diagnosed with advanced melanoma, the deadliest known form of skin cancer. Many patients have become resistant to vemurafenib, a treatment used to combat the disease, but scientists may have found a solution by blocking proteins.

The research, published in Nature Communications, found that the MLK family of four enzymes 'undoes' the tumour-shrinking effects of vemurafenib. 

Around half of aggressive skin cancers or metastatic melanomas are caused by a fault in the cell-growth gene BRAF, which forces the signal telling cells to multiply to be permanently switched on.

The scientists at the Cancer Research UK Manchester Institute, based at the University of Manchester knew that, although vemurafenib blocks BRAF - therefore stopping cancer cell growth - the cells usually find a different way to turn the pathway back on. This prevents the drug from working and most metastatic melanoma patients stop responding within six months, causing a relapse of the aggressive disease.

The new study found that MLK enzymes can be responsible for re-activating the BRAF pathway, even when a treatment of vemurafenib has been given. It is hoped that by blocking these enzymes, resistance to vemurafenib can be prevented so cancer cells remain vulnerable to the drug.

Some patients also have gene mutations, causing them to become resistant to vemurafenib more quickly.

Dr John Brognard, from the Cancer Research UK Manchester Institute and lead author of the study, described the research as "exciting" as it reveals that melanoma cells have enzymes "acting like a manual override switch to regenerate growth signals" even after treatment is given to switch them off.

He added that this family of enzymes are turned on in metastatic melanomas, which are not caused by BRAF. This, according to the lead author, suggests they may serve as a new target in metastatic melanomas for which there are limited treatment options.

"The good news is there are already experimental drugs that can block these enzymes in the laboratory. And this research paves the way for the development of drugs to overcome vemurafenib resistance in melanoma patients," said Dr Brognard.