IGF1R and cancer: We and others demonstrated that antibody-induced IGF-1R downregulation stabilizes a biased receptor conformation that preferentially activates kinase-independent β-arrestin 1 signaling (Figure 2 and Table 1) and not only promotes MAPK enhancement but also represses the tumor suppressor p53 activation (Figure 2), which could explain the cancer cell survival, the augmented metastatic potential, and the overall limited response to this single agent therapy [10,39,98,99,182].