Breakthrough Hope for Melanoma Blocker – RA Drug Singled Out from Thousands Screened

“We are very optimistic that this research will lead to novel treatments for melanoma tumors which, working alongside other therapies, will help to stop them progressing.”

A breakthrough discovery by researchers at the University of East Anglia and Children’s Hospital Boston promises an effective new treatment for one of the deadliest forms of cancer.

As reported Mar 24 in the journal Nature(1), they found that leflunomide – a drug commonly used to treat rheumatoid arthritis – also inhibits the growth of malignant melanoma.

Melanoma is a cancer of the pigment cells in our skin. It is the most aggressive form of skin cancer and, unlike most other cancers, incidence of the disease is increasing. More than 68,000 patients in the US and 10,000 in the UK are diagnosed with melanoma each year.

If caught early, surgery can be used to safely remove the tumor but the chances of survival for patients whose tumor is already spreading are very low. Around 9,000 people in the US and 2,000 in the UK die annually from malignant melanoma because the cancer has returned after being removed surgically.

Four Steps to Hope for Complete Melanoma Block

• UEA scientists Dr. Grant Wheeler and Dr. Matt Tomlinson conducted a rigorous screen of thousands of compounds, looking for those that affect the development of pigment cells in tadpoles. They identified a number of compounds that affected pigment cell development.

• They then showed, with their US collaborators at Children’s Hospital Boston, that leflunomide significantly restricts tumor growth in mouse models.

• And when leflunomide is used in combination with PLX4720 (a promising new melanoma therapy currently undergoing clinical trials), the effect was even more powerful – leading to almost complete block of tumor growth.

• The next stage is for human clinical trials to be conducted into the use of leflunomide to fight melanoma.

Because leflunomide is already licensed to treat arthritis, the clinical trial process should be faster than usual and a new treatment for melanoma could be broadly available within around five years.

“This is a really exciting discovery – making use of an existing drug specifically to target melanoma,” says Dr. Wheeler.

“Deaths from melanoma skin cancer are increasing and there is a desperate need for new, more effective treatments,” Dr. Wheeler explains. “We are very optimistic that this research will lead to novel treatments for melanoma tumours which, working alongside other therapies, will help to stop them progressing.”

The Power of Large-Scale Compound Screening

The novel work, which was partly funded by the Biotechnology and Biological Sciences Research Council, highlights the strength of carrying out large screens of compounds in developmental model systems such as the Xenopus tadpole used at UEA and the zebrafish used at Childrens Hospital Boston.

The hope is that this approach will lead to the discovery of further compounds to treat different diseases in the future.

“Cancer is a disease not only of genetic mutations, but also one determined by the identity of the cell in which the tumor arises,” explains lead author Dr. Richard White at Children’s Hospital Boston and Harvard Medical School. “By studying cancer development in zebrafish and frogs, we gain a unique insight into the very earliest changes that occur in those cells.”


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“>“DHODH modulates transcriptional elongation in the neural crest and melanoma”

Source: University of East Anglia press release, Mar 23, 2011

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