Intriguingly, increased receptor tyrosine kinase (RTK) signaling through for instance IGF-1R, PDGFR, or EGFR is also frequently found in relapsed melanomas (Nazarian et al., 2010; Villanueva et al., 2010; Girotti et al., 2013; Sun et al., 2014), and this can lead to ERK activation via classical pathway activation through RAS and CRAF (Figure 2). The gene discussed is EGFR; the disease is melanoma.