While this underscores the importance of the RAF-MEK-ERK pathway in melanoma proliferation and survival, in the last few months several examples of resistance mechanisms have been reported that do not rely on sustained ERK signaling, indicating that other “ERK-independent” pathways can compensate for loss of ERK activity and can maintain the tumorigenicity of BRAF V600E melanoma in the absence of ERK activation. This evidence concerns the gene MAP2K7 and melanoma.