Scientists develop drugs to block skin cancer protein

Cancer Research UK

Scientists have developed a potent group of potential drug candidates to treat skin cancer, according to a study in the Journal of Medicinal Chemistry today (Thursday).

The study - funded by Cancer Research UK, The Institute of Cancer Research (ICR) and the Wellcome Trust - reveals a new class of potential drug candidates that are designed to treat malignant melanoma - the deadliest form of skin cancer.

This team previously showed that a protein called BRAF, which is mutated in 50 to 70 per cent of human melanomas, is responsible for driving the growth of melanoma cells.

The chemicals they have developed, called pyridoimidazolones, block the activity of the mutated BRAF protein and so inhibit the growth of melanoma cells.

Highly targeted drugs like this new group act selectively on melanoma cells with mutated BRAF.

Treatments like this will lead to fewer side effects and should be more effective at stopping and killing cancer.

Lead author Professor Caroline Springer, from the ICR, said: "In our studies on cells from human cancer samples, we have developed some exciting potential treatments that could soon be assessed in patients in the clinic.

"They're so effective because they deliver a knock out blow to a specific mutant protein that we know goes wrong in more than 50 per cent of skin cancers.

"Targeting mutant key proteins in this way is a new and important approach to treating cancer - we hope that this field of research will yield a new generation of drugs that are more effective and selective for cancer cells.

"We hope to choose the most promising compounds soon for assessment in early clinical trials for patients with advanced skin cancer."

BRAF is mutated in around two per cent of all cancers - including 50 to 70 per cent of melanomas, 35 per cent of ovarian cancers, 35 per cent of thyroid cancers and 10 to 15 per cent of bowel cancers.

When mutated, the gene causes a change in the BRAF protein, which allows cells to grow uncontrollably into cancerous tumours.

Dr Lesley Walker, Cancer Research UK's director of cancer information, said: "The results from this study are certainly impressive.

"Targeting specific proteins produced by mutated genes in cancer is an exciting area of research, so we're keen to see how these drugs fare in trials in cancer patients."

ENDS

For media enquiries please contact the Cancer Research UK press office on 020 7061 8300 or, out-of-hours, the duty press officer on 07050 264 059.

Notes to Editor

* Pyridoimidazolones as novel potent inhibitors of v-Raf murine sarcoma viral oncogene homolog B1 (BRAF). Niculescu-Duvaz et al. Journal of Medicinal Chemistry. April 2009.

About skin cancer

In the UK around 9,500 cases of malignant melanoma - the most deadly form of skin cancer - are diagnosed each year.

More than 2,300 people die from skin cancer each year in the UK.

Sun exposure is the main cause of malignant melanoma and non-melanoma skin cancers.

Scientists think that around one in 10 cases of melanoma may be linked to inherited faulty genes. For the small number of families who carry these genes, sun protection is even more important. People who have had melanoma and have a parent who has had melanoma have a risk of getting another melanoma that is 30 times higher than the general population.