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Arthritis drug could help beat melanoma skin cancer

Visit UEA - University of East Anglia website

24 March 2011

Research by BBSRC funded scientists at the University of East Anglia (UEA) to understand the fundamental biology of cell development has led to a breakthrough discovery that promises an effective new treatment for one of the deadliest forms of cancer.

The work, which was done jointly with Children's Hospital Boston is reported today (23 March) in the journal Nature. The researchers found that leflunomide - a drug commonly used to treat rheumatoid arthritis - also inhibits the growth of malignant melanoma.

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. (See www.uea.ac.uk/mac/comm/media/press/2009/jan/tadpoles.) They identified a number of compounds that affected pigment cell development and have now shown with their US collaborators at Children's Hospital Boston that leflunomide significantly restricts tumour 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 tumour growth.

The next stage is for clinical trials to be conducted into the use of leflunomide to fight melanoma. Because leflunomide is already licensed to treat arthritis, this process should be faster than usual and a new treatment for melanoma could be available within around five years.

"This is a really exciting discovery - making use of an existing drug specifically to target melanoma," said Dr Grant Wheeler, of UEA's School of Biological Sciences.

"Deaths from melanoma skin cancer are increasing and there is a desparate need for new, more effective treatments. 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."

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

This work 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.

ENDS

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Notes to Editors

'Inhibitors of DHODH suppress neural crest development and melanoma growth via modulation of transcriptional elongation' by R White (Children's Hospital Boston), S Ratanasirintrawoot (Children's Hospital Boston), C Lin (MIT), P Rahl (MIT), J Cech (Children's Hospital Boston), C Burke (Children's Hospital Boston), E Langdon (Children's Hospital Boston), M Tomlinson (UEA), J Mosher (University of Michigan), C Kaufman (Children's Hospital Boston), F Chen (Children's Hospital Boston),H Long (Cambridge University), M Kramer (Genzyme Corporation), S Datta (Children's Hospital Boston), D Neuberg (Children's Hospital Boston), S Granter (Children's Hospital Boston), R Young (MIT), S Morrison (University of Michigan), G Wheeler (UEA) and L Zon (Children's Hospital Boston) is published in the March 24 edition of Nature.

For further information or to arrange pictures or interviews, please contact Simon Dunford at the University of East Anglia Communications Office: +44 (0)1603 592203 or s.dunford@uea.ac.uk. The paper is available as a PDF file on request.

Case study: Advanced melanoma (grade 4) patient Janet Pearce is available for interview.

To contact the US research team, please email Rachel.blumenthal2@childrens.harvard.edu or telephone 617-919-2009.

About BBSRC

BBSRC is the UK funding agency for research in the life sciences. Sponsored by Government, BBSRC annually invests around £470M in a wide range of research that makes a significant contribution to the quality of life in the UK and beyond and supports a number of important industrial stakeholders, including the agriculture, food, chemical, healthcare and pharmaceutical sectors.

BBSRC provides institute strategic research grants to the following:

  • The Babraham Institute
  • Institute for Animal Health
  • Institute of Biological, Environmental and Rural Sciences (Aberystwyth University)
  • Institute of Food Research
  • John Innes Centre
  • The Genome Analysis Centre
  • The Roslin Institute (University of Edinburgh)
  • Rothamsted Research

The Institutes conduct long-term, mission-oriented research using specialist facilities. They have strong interactions with industry, Government departments and other end-users of their research.