In this context, fast proliferation rates of cancer cells enhance DNA replication stress (Gaillard et al., 2015), and we have recently demonstrated that HMGA2 broadly protects hydroxyurea (HU)‐induced stalled replication forks from collapse into genotoxic DSBs in human cancer and stem cells, thus implying that HMGA2 is also involved upstream of DNA repair processes as a first line of defense to prevent genome instability (Ahmed et al., 2019; Yu et al., 2014). This evidence concerns the gene HMGA2 and cancer.