Importantly, in contrast to HCT116 cells, co-inhibition of CDK12 and P-TEFb was significantly less toxic for a non-transformed colorectal epithelial cell line CCD 841 CoN that encodes wild-type p53 (Supplementary Figure S4B), suggesting that cancer cells exhibit heightened dependence on CDK12 and P-TEFb. This evidence concerns the gene TP53 and cancer.