Finally, we leveraged the flexibility of in vitro propagation and syngeneic in vivo allografting of sarcoma EPO-GEMMs to apply some of our models to small-molecule testing. NTRK inhibitor therapy with first (Larotrectinib) and second generation (Repotrectinib) agents showed specific and significant activity in NTRK-Mono and NTRK-Pleo cell lines in vitro, comparable to response rates in a rare patient-derived cell model acquired from a patient suffering from NTRK-driven Inflammatory Myofibroblastic Tumor (IMT) (Fig. 6f). Here, EPO is linked to sarcoma.