On the basis of the successes of CDK4/6 inhibitors in dedifferentiated liposarcoma (Lin et al. 2020), as well as the current clinical data supporting the use of CDK4/6 inhibitors in subsets of sarcoma primarily driven by CDK4/6 deregulation (Hsu et al. 2022), available CDK4/6 small molecule inhibitors targeting the E2F pathway may be promising for the treatment of variants of ES including the BCOR–CCNB3 fusion subset. This evidence concerns the gene BCOR and sarcoma.