The neural crest is a group of embryonic stem cells that pinch off from the early spinal cord as it takes shape. Neural crest cells end up in diverse locations throughout the body, but most become melanocytes – skin cells that produce the protective pigment known as melanin. Later in life, cancerous melanoyctes are responsible for the least common but most deadly form of skin cancer – melanoma. The process of melanoma tumor initiation is analogous to the original embryonic events that lead to melanoycte differentiation. Scientists have known for several years that most of the mutations associated with melanoma occur in a gene named BRAF, but how those mutations interact with the cellular programs involved in neural crest development were less well understood. After testing multiple drugs in zebrafish, Harvard Stem Cell Institute Principal Faculty Member Leonard Zon and colleagues identified a small molecule that inhibits neural crest development in zebrafish embryos and blocks human melanoma tumor growth. Leflunamide, a common anti-arthritis drug, could be used in concert with BRAF inhibitors to strengthen melanoma therapy.

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 518 – 522.