These results are in resonance with previous literature describing gain-of-function mutations in TP53 that lead to enhanced CDC7-dependent replication initiation in LUAD,15 enrichment for RB1 and TP53 mutations in CDC7-high LUAD,23 and increased sensitivity to CDC7 inhibition in TP53-mutant breast carcinomas.39 We extend these observations, demonstrating that TP53- and RB1-deficient adenocarcinomas of the lung and prostate have increased sensitivity to CDC7 inhibition, providing a rationale to target CDC7 as a means to constrain histological transformation. Here, RB1 is linked to lung adenocarcinoma.