In Ewing’s sarcoma, PLK4 inhibition by CFI-400945 or centrinone leads to cell death and G2/M arrest; CFI-400945 treatment produces polyploidy [82]. CFI-400945 treatment shows antitumor activity in uterine leiomyosarcoma with DNA repair deficits and in combination with ataxia telangiectasia mutated (ATM) inhibitor, AZD0156, synergizes antitumor effects [56]. The gene discussed is PLK4; the disease is Ewing sarcoma.