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Collectively, these results uncover mechanisms behind deleterious effects of TOP2 abortive activity during transcription, with relevant implications for chemotherapy.Recently, a transcriptome-based consensus molecular subtype (CMS) classification of colorectal cancer (CRC) has been established, which may ultimately help to individualize CRC therapy. However, the lack of animal models that faithfully recapitulate the different molecular subtypes impedes adequate preclinical testing of stratified therapeutic concepts. Here, we demonstrate