Date Published: 23 April 2009

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% 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% 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 2% of all cancers – including 50 to 70% of melanomas, 35% of ovarian cancers, 35% of thyroid cancers and 10 to 15% 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."


Source: Cancer Research UK.

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