Lab tests suggest arthritis drug could slow melanoma skin cancer growth

In collaboration with Adfero

In research published in Nature, an international team of scientists have shown that an existing rheumatoid arthritis drug can slow down the growth of malignant melanoma, the deadliest form of skin cancer. The research was done in zebrafish and mice.

Researchers at the University of East Anglia (UEA) and Children's Hospital Boston in the US found that the drug leflunomide slowed down the growth of tumours over a short period of time.

Drs Grant Wheeler and Matt Tomlinson worked with their US collaborators to test more than 2,000 chemicals, to find ones that might halt the disease. The best candidate blocked a protein also known to be targeted by the drug leflunomide, commonly used to treat arthritis.

The researchers showed that a combination of leflunomide and a promising experimental melanoma therapy called PLX4032 was particularly effective at blocking tumour growth over 12 days.

PLX4032 is currently being tested in clinical trials and is designed to block a protein called BRAF, which was shown by Cancer Research UK scientists to be overactive in around half of all melanomas.

Dr Wheeler, from the University of East Anglia's School of Biological Sciences, said: "This is a really exciting discovery - making use of an existing drug specifically to target melanoma.

"Deaths from melanoma skin cancer are increasing and there is a desperate 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."

But, Cancer Research UK-funded scientist Professor Richard Marais at The Institute of Cancer Research sounded a more cautious note. "This work represents a very interesting new experimental approach to melanoma, but obviously there's a long way to go before we can start using these sorts of combinations in patients. We need to do a lot more preclinical studies and a lot more studies in appropriate models."

Meanwhile, a second study in Nature, from the same US group that worked with the UEA team, has shed light on a molecule that appears to influence the growth of melanoma.

Again working with zebrafish, researchers led by Professor Leonard Zon, discovered that a histone-methylating enzyme called SETDB1 cooperates with BRAF faults in melanoma cells to significantly speed up the development of the disease.

References

  • White, R., Cech, J., Ratanasirintrawoot, S., Lin, C., Rahl, P., Burke, C., Langdon, E., Tomlinson, M., Mosher, J., Kaufman, C., Chen, F., Long, H., Kramer, M., Datta, S., Neuberg, D., Granter, S., Young, R., Morrison, S., Wheeler, G., & Zon, L. (2011). DHODH modulates transcriptional elongation in the neural crest and melanoma Nature, 471 (7339), 518-522 DOI: 10.1038/nature09882
  • Ceol, C., Houvras, Y., Jane-Valbuena, J., Bilodeau, S., Orlando, D., Battisti, V., Fritsch, L., Lin, W., Hollmann, T., Ferré, F., Bourque, C., Burke, C., Turner, L., Uong, A., Johnson, L., Beroukhim, R., Mermel, C., Loda, M., Ait-Si-Ali, S., Garraway, L., Young, R., & Zon, L. (2011). The histone methyltransferase SETDB1 is recurrently amplified in melanoma and accelerates its onset Nature, 471 (7339), 513-517 DOI: 10.1038/nature09806