Myxofibrosarcoma and undifferentiated pleomorphic sarcoma (UPS) lack specific molecular underpinnings, show high rates of metastasis, and display limited responsiveness to current therapies, making them challenging cancers both to treat and to study. It has been noted that MFS and UPS frequently lose function of the tumor suppressor genes RB1 and TP53 In this issue of Cancer Research, Li and colleagues demonstrate that proliferation in RB1- and TP53-deficient MFS and UPS depends on SKP2; inhibiting SKP2 with the neddylation inhibitor, pevonedistat, halts tumor growth in a panel of patient-derived xenografts. This renders the oncogenic protein SKP2 a promising therapeutic target.See related article by Li et al., p. 2461.
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