The use of specific inhibitors for Neddylation components, such as UBE2M inhibitors [42] or MLN4924, which induced cell cycle arrest in human osteosarcoma [117], may be attractive new avenues for the treatment of the ST_EPN_RELA subtype but the development of more specific inhibitors of CRLs is warranted to benefit EPN patients. This evidence concerns the gene UBE2M and osteosarcoma.