RB1 and cancer: Recent studies have further demonstrated RB1′s necessity in DNA double-strand break repair via canonical non-homologous end-joining (cNHEJ), wherein RB1 interacts with NHEJ components XRCC5 and XRCC6 [29], suggesting RB1 loss as a potential driver of structural genomic instability, contributing to cancer somatic heterogeneity and evolution.