However, continuous activation of DDR constitutes a sustained “pressure” eventually leading to the mutation of the TP53 gene and loss of the anti-tumor barriers elicited by DDR, providing an explanation for the extremely high rate of TP53 mutations in sporadic solid tumors and initiation of DDR in advanced cancers (Halazonetis et al., 2008; Negrini et al., 2010). The gene discussed is TP53; the disease is cancer.