FIGURE 4.

Therapeutic interventions tested in the 146 selected phase‐I/II trials in recurrent or refractory Ewin sarcoma. (A) Therapeutic intervention type. (B) Therapeutic intervention over time between 2005 and 2018. (C) Targeted pathways in trials for targeted therapy drugs (Orange) and immunotherapy drugs (Green). Signaling pathway: Pi3k/Akt/mTOR, Igfr/ir, Raf‐braf, Tgfβ1, Sonic hedgehog, Alk, Errb, Ntrk, and Pak4. Multisignaling pathway: any multi‐tyrosine kinase Inhibitor. Epigenetic: histone deacetylase, histone demethylase‐Inhibitor, and ezh2. DNA repair: parp inhibitors. Antiangiogenic: vegf and fgf/fgfr. Transcription: anti Ews‐fli1. Metabolism: Aldh, Ascorbate, and Statin. Cell cycle: cdk4/cdk6. Immunity/inflammation: Anti‐COX2. Other: molecular‐targeted trials and Xpo‐1. Checkpoint inhibitors: antibody against PD1, PDL1, CTLA4. Adoptive cell therapy: immunotherapy that uses the patient's own T cells after in vitro treatment. Antiangiogenic antibody targeted VEGF. Anti‐inflammatory immunotherapy: IL2 aerosol. 12 years old