Disrupting EWS–FLI1:PARP1’s interaction with the PARP1 inhibitor olaparib suppressed the growth of ES cells, primary mouse tumor xenografts, and tumor metastases, while tumorigenesis in an EWS–FLI1-induced ES mouse xenograft model was completely inhibited by combination of olaparib and the second-line chemotherapeutic drug temozolomide. The gene discussed is PARP1; the disease is neoplasm.