Metastatic cutaneous melanoma is an aggressive cancer that is resistant to current therapy. The mutations in epidermal melanocytes that lead to cancer are often propelled by changes in the oncogenes encoding RAS, RAF, MEK, ERK or PI3K. Here, Christina Michailidou and colleagues show that expression of mutant RAS (V12RAS) in zebrafish produces a similar phenotype to familial atypical mole and melanoma syndrome (FAMM) in humans. Similarities include variable melanocyte morphology and growth, and the spontaneous formation of invasive melanoma. Using this model, they demonstrate that blocking PI3K, an effector of the RAS signaling pathway, is sufficient to inhibit melanoma formation.
