'Drug holidays' improve response to key skin cancer drug in mice

In collaboration with the Press Association

Melanoma skin cancers that develop resistance to the drug vemurafenib also become "addicted" to it, fuelling their resistance.

In lab tests, scientists in California and Switzerland showed that removing the drug for a short period of time - rather than giving a continuous dose - caused such vemurafenib-dependent tumours to shrink.

The finding could help improve survival for patients with late-stage melanoma, the most deadly skin cancer, according to research published in Nature.

Professor Mark Middleton, director of Cancer Research UK's Experimental Cancer Medicine Centre at Oxford, said: "We still need to test the idea in the clinic, but these results suggest a way in which this important new treatment might be able to increase the benefit to patients and their families.

"It also offers the possibility of more cost-effective treatment, with fewer side effects, because patients would spend some of the time off vemurafenib."

Vemurafenib, also known as Zelboraf, is one of the first new drugs to be made available to patients with melanoma for over a decade. It works by targeting a faulty protein called BRAF, which is found in around half of all melanomas.

The researchers from the University of California, San Francisco (UCSF) and Novartis Institutes for Biomedical Research found that tumours that become resistant to vemurafenib treatment do so by making more BRAF - the very thing the drug is intended to targeted

They then deduced that drug-resistant tumours might stop growing when they stopped giving vemurafenib.

As predicted, in mice with drug-resistant melanomas no longer treated with vemurafenib the tumours shrank.

Study leader Dr Martin McMahon, from UCSF, said: "Remarkably, intermittent dosing with vemurafenib prolonged the lives of mice with drug-resistant melanoma tumors," said.

The research raises the possibility that so-called "drug holidays" could extend vemurafenib's effectiveness in humans, although clinical trials have yet to be conducted.

Professor Richard Marais, Director of Cancer Research UK's Paterson Institute at the University of Manchester, was part of a Cancer Research UK-funded team that discovered the BRAF faults in melanoma. He described vemurafenib as "an exciting drug and one of the success stories of cancer research".

"It's not a cure for melanoma but can give people valuable extra months," he added.

More than 12,800 people in the UK are diagnosed with melanoma skin cancer every year and around 2,200 die from the disease.

Professor Marais added: "This new study is exciting because it suggests a way to combat the evolution of drug resistance in melanoma patients using the drugs we already have, rather than having to develop new ones. It will be interesting to see if these lab results are mirrored in clinical trials."

Copyright Press Association 2013

References

  • Thakur, M. D. et al. Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance. Nature doi:10.1038/nature11814