Fan et al. found that methylene blue prevented SHP2 from binding with Y248-phosphorylated PD-1 and therefore enhanced the tumor-killing effect of CTLs.264 In addition, inducing the degradation and ubiquitination of SHP2 through its intracellular E3 ligase, FBXW7, was an outstanding approach that interrupted the downstream signaling pathways of SHP2, such as ERK and IFN I.265 Overall, although this approach is still in its infancy, it is a promising strategy for selective and effective inhibition of the effects of SHP2 (Fig. 7). The gene discussed is PTPN11; the disease is neoplasm.