Adding lung cancer drugs to targeted melanoma treatment could increase survival for certain patients, according to research published in Cancer Discovery today.
Scientists at Cancer Research UK’s Paterson Institute at The University of Manchester showed that lung cancer drugs such as gefitinib (Iressa) can override resistance to new targeted therapies for melanoma, called BRAF inhibitors.
The first BRAF inhibitor, vemurafenib (Zelboraf), was approved for patients on the NHS in 2012, and others are currently in development. They work by targeting a faulty version of the BRAF protein, found in more than half of all melanomas as well as some other types of cancer.
But patients often become resistant to BRAF inhibitors after a short time and their disease returns, leaving them without further treatment options.
Now scientists have found that treating BRAF inhibitor-resistant cancer cells or tumours with the drugs gefitinib or dasatinib, which block a different biological pathway, can halt their growth.
Lead author, Professor Richard Marais, director of Cancer Research UK’s Paterson Institute, said: “This exciting research shows that two drugs can be better than one in beating this deadly disease.
“If these findings are confirmed in larger studies, combining two drug types could provide an effective new treatment for skin cancer patients for whom the only existing targeted treatment available – vermurafenib – no longer works.
“This is a vital step to understand how to treat the disease more effectively but there is still a lot to do. We hope that this work accelerates progress that will ultimately increase survival from skin cancer.”
Around 12,800 people in the UK are diagnosed with malignant melanoma each year and there are around 2,200 deaths from the disease.
Dr Julie Sharp, Cancer Research UK’s senior science information manager, said: “These new results builds on our work on the BRAF gene, which has led to the development of important new drugs for melanoma.
“This fundamental research into the biology of cancer is leading directly to new treatments and we hope that this latest study will bring forward more effective approaches for treating melanoma, which we urgently need. This is the kind of work that the new Manchester Cancer Research Centre excels at – bringing together a wide range of expertise to revolutionise cancer treatment.”
Professor Marais’ team is part of the Manchester Cancer Research Centre (MCRC), which is a partnership between Cancer Research UK, The Christie and The University of Manchester. A new campaign, “More Tomorrows”, is fundraising to build a centre for MCRC scientists to work together on treatments for cancer.
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Inhibiting EGF receptor or SRC family kinase signalling overcomes BRAF inhibitor resistance in melanoma. Cancer Discovery. Maria R Girotti et al.
NICE has approved gefitinib for the first-line treatment of locally advanced or metastatic non-small cell lung cancer.
Dasatinib (Sprycel) is used to treat some types of leukaemia, but is not currently approved by NICE for use on the NHS except through the Cancer Drugs Fund.
Some melanoma cancer cells respond to BRAF inhibitor resistance by turning on a biological pathway called EGF signalling. This drives cancer via a different cell signalling route. The combination of BRAF inhibitors and drugs targeting EGF signalling, including gefitinib and dasatinib, blocks these two faulty cell signalling routes simultaneously, so the cancer cells stop growing.