A functional, chemical genomic and super-enhancer screen identified CDK4 as a potential vulnerability in Ewing sarcoma, with pharmacologic inhibition using CDK4/6 inhibitors leading to cell death in Ewing sarcoma preclinical models, supporting exploration of CDK4/6 inhibitors as a therapeutic approach for Ewing sarcoma patients [42,43]. Here, CDK4 is linked to Ewing sarcoma.