MYC oncogenes are implicated in various cancers, but are considered difficult to 'drug' as they encode transcription factors. Toyoshima et al. used a functional genomic screen to identify genes that, when expressed with oncogenic MYC, provide a synthetic lethal interaction. Several genes were identified that selectively induced the accumulation of DNA damage in MYC-expressing cells. Validation studies showed that inhibition of casein kinase 1χ, expression of which correlated with MYC expression in human cancers, prevented the growth of MYC-amplified neuroblastoma xenografts.