The reasons include: (1) dysregulated coordination between cell cycle progression and DNA replication due to the loss of tumor suppressors, such as p53 and Rb, and the overexpression of many oncogenes, such as Myc and Ras; (2) mutations in genes encoding the DNA damage response (DDR) and DNA repair proteins, such as BRCA1 and BRCA2. The heightened replication stress in many cancers has been hypothesized to be their Achilles’ heel and can potentially be used as a target for cancer treatment (Cybulla and Vindigni, 2022; da Costa et al., 2022). The gene discussed is RB1; the disease is cancer.