Tumour cells share many characteristics with embryonic cells and it is thought that they acquire these characteristics through activation of developmental pathways. On p. , Leonard Zon and co-workers develop a screening strategy to look for pathways that are common to embryogenesis and tumorigenesis in zebrafish. The researchers first evaluate gene expression in transgenic zebrafish embryos that express an inducible mutated RAS gene – RAS family members are the most commonly mutated oncogenes in human cancers and the RAS pathway is a key developmental pathway during embryogenesis. The researchers then use one of the genes that is upregulated by RAS expression to screen for small molecules that interfere with RAS signalling during embryogenesis. Finally, they show that two of the retrieved inhibitors suppress the growth of a zebrafish KRAS-induced embryonal rhabdomyosarcoma and of an NRAS-induced human rhabdomyosarcoma cell line. Together, these results demonstrate that common pathways are activated by RAS during embryogenesis and tumorigenesis and establish zebrafish embryos as a platform for anti-cancer drug discovery.
