Consistent with the notion that cancer cells may share a common mechanism for resistance to different anti‐cancer drugs,[29] among top screen hits, RSK2 and TP53BP1 mutants restrain 5‐FU‐induced apoptosis by antagonizing 5‐FU‐triggered transcriptomic alterations, with a high proportion of overlapping target genes (Figure 3). Here, RPS6KA3 is linked to cancer.