PTPN11 and cancer: Recently, SHP2 signaling response activation to the inhibitors of RAS downstream effectors has been reported in multiple cancer types, and combined targeting of RAS downstream effectors, especially for MEK inhibitors and SHP2, generated significant synthetic effects on tumor growth (Fedele et al., 2018; Wong et al., 2018; Ahmed et al., 2019; Lu et al., 2019).