Considering the positive role of Shp2 in Ras-dependent Erk activation (Ras-to-Erk), as well as in oncogenic Ras-to-Erk [21, 22] and target therapy resistance [23], small molecules to inhibit the bivalent roles of Shp2 have been developed as novel anti-cancer therapeutic agents [24]. Here, MAPK1 is linked to cancer.