Melanomas commonly stop responding to targeted therapies and a new study helps explain why. The researchers linked resistance to BRAF and MEK inhibitors in people with two genetic abnormalities: extra copies of BRAF-V600E, the most common melanoma mutation, as well as a new mutation called MEK2-Q60P. Encouragingly, the researchers also found that adding a third treatment (a PI3K inhibitor) to the mix makes melanomas stop growing in mice. While the team cautions that the solution is unlikely to be as simple of a triple inhibitor treatment for people, this work could help researchers find ways of overcoming drug resistance in melanomas.