For example, the combination of IGF-1R antibodies with mTOR inhibitors has been evaluated in ES, with the rationale that mTOR inhibitors can induce AKT phosphorylation and signaling via an IGF-1R dependent mechanism; (112) given this dependence, it was thought that the combination of an IGF-1R antibody and mTOR inhibitor would have the potential to overcome the resistance seen when either was given as monotherapy. Here, IGF1R is linked to Ewing sarcoma.