Investigating repurposed drugs to decrease the progression of Ewing’s sarcoma

Ewing’s sarcoma (EwS) is the second most common primary bone sarcoma in people aged 30 and under. The most common underlying cause is the EWS-FLI1 gene fusion, which drives expression of Neuropeptide-Y (NPY). Under normoxic conditions, NPY acts upon Y1/Y5 receptors to activate cell death but in EwS there is tumour hypoxia causing increased expression of dipeptidyl peptidase 4 (DPP-4), which truncates NPY to NPY3-36. Tumour-associated macrophages (TAMs), which have been established as a poor prognostic marker in EwS, may also have a role in DPP-4 and NPY metabolism. This project aim is to determine the expression of NPY, NPY3-36., DPP4, Y1 and Y5 receptors in Ewing’s sarcoma and to test the effect of macrophage-secreted DPP4 upon EwS cells and to attempt to block any pro-tumoral effects with DPP4 inhibitors including gliptins.