Lab tests suggest panRAF inhibitor may be effective in melanoma patients no longer responding to existing treatments.
A drug that scientists believe could revolutionise treatment for advanced skin cancer is to be trialled in the UK.
Laboratory tests suggest that the drug, known as a pan-RAF inhibitor, is likely to be effective in melanoma patients who are no longer responding to existing treatments. It might also help people with a strain of cancer that cannot be treated with standard drugs.
Melanoma, or malignant skin cancer, affects around 13,000 people and causes more than 2,000 deaths in the UK each year. Surgery is always the first treatment option. But in more advanced cases, patients are given drugs that suppress faulty versions of a protein called BRAF, which fuels the growth of about half of all melanomas.
While BRAF inhibitors are initially very effective, the cancers generally become resistant to them within a year. The new drugs, which target a wider range of biological pathways, have been shown to halt the growth of resistant tumours. They also appear to work against the 20-25% of melanomas driven by a different defective protein, RAS.
Prof Caroline Springer, from the Institute of Cancer Research in London, who co-led a study of the new drugs published in the journal Cancer Cell, said: “Melanomas often respond initially to the current generation of treatments, but they inevitably acquire resistance to them and there is a desperate need for more effective options.
“Our new inhibitors are the first in a new family of drugs that attack cancers without allowing them the get-out clause of drug resistance, by blocking multiple cancer proteins at once. We are very hopeful that clinical trials from this series of new inhibitors will begin very soon – and that they will ultimately become new first- or second-line options for patients who, at the moment, exhaust all the available treatments and end up with fatal disease.”
Prof Richard Marais, director of the Cancer Research UK Manchester Institute, based at the University of Manchester, said: “Our laboratory study showed that these new drugs deliver multiple blows to cancer by hitting several cell survival routes at once. It’s a step on from the drugs that are currently available, which can’t multitask in this way.
“The next step is testing this family of drugs in clinical trials to establish that they are both safe and effective in cancer patients, potentially providing urgently-needed new treatments for patients who have run out of options.”
The phase-I trial is likely to involve a small number of patients and focus mainly on safety and dosage, although it might also produce some data about the drug’s effectiveness.
Assuming the results are positive, further larger trials will look more closely at how well the drug performs. Few details of the trial are available at this stage, and the number of patients due to take part is yet to be determined. But Springer said funding had been agreed and an application made for ethical approval.
She added: “We’re all very excited and very hopeful, because it’s very important to have different therapies to offer patients who have become resistant to existing treatments.”
Patients will be given one specific drug that was chosen from hundreds of candidates after rigorous testing. In the laboratory study published in Cancer Cell, two drugs codenamed CCT 196969 and CCT 241161 were tested. Both suppressed drug-resistant tumours from patients grown in mice without significant side effects.
Dr Richard Seabrook, head of business development at the Wellcome Trust, which co-funded the research together with Cancer Research UK, said: “Malignant melanoma is the fifth most common cancer in the UK, with over 13,000 people diagnosed in 2011. Doctors already have frontline drugs to treat melanoma, but many patients gradually develop resistance to them and are left with few other treatment options.
“This research, which discovered how two newly developed compounds could treat drug-resistant skin cancer, may give hope to the thousands who find themselves in this situation.”
Source: Press Association