UK scientists have identified a protein which plays a key role in restricting the body’s natural defences against malignant melanoma – the most serious form of skin cancer.

The discovery by the team at Nottingham Trent University could have broad implications for the future treatment of the disease, which has quadrupled in the UK in the last 30 years.

The researchers – writing in the journal Cell Death and Disease – have found a protein which promotes malignant melanoma’s resistance to interferon alpha, which is secreted by the blood cells as part of the body’s natural immune response to cancer.

Interferon-alpha, which stops cancer cells growing and multiplying, is used for the treatment of patients with skin cancer, but has only been shown to result in a slight improvement of relapse-free and overall survival.

Now the scientists, from the university’s John van Geest Cancer Research Centre, have identified how this ‘HAGE’ protein – which presents itself exclusively in cancer cells during many cases of malignant melanoma – interrupts the body’s protection process.

They have found that the protein works to reduce the expression of the ‘tumour suppressor’ promyelocytic leukaemia protein after it is induced by interferon-alpha to help tackle the spread of the disease.

By inactivating the HAGE protein, combined with interferon treatment, the researchers were able to reduce tumour growth in laboratory tests by as much as three quarters (75%).

“Our findings suggest that targeting the HAGE protein could have major implications for future cancer therapies and the treatment of malignant melanoma,” said Dr Tarik Regad of Nottingham Trent University’s John van Geest Cancer Research Centre.

He said: “We knew that tumours developed mechanisms of resistance to anti-tumour activities in the body, but before now we didn’t fully understand the factors behind this specific resistance to interferon-alpha treatment.

“Now, as a result of this study, we have identified that the protein HAGE is preventing the anti-tumour effect of interferon-alpha in malignant melanoma. This is very exciting data and could help to make a real impact in the continued fight against this disease.

“Over the last 30 years, rates of malignant melanoma in the UK have risen faster than any of the other top ten cancers, and it is vital that new methods are sought to tackle it.”

Sun exposure is the main cause of malignant melanoma – in the UK around 11,100 cases each year are linked to excessive exposure to sunlight and use of sunbeds.

 

Source: Nottingham Trent University