BUB signaling in cancer and molecular insights into targeted therapies

The Spindle Assembly Checkpoint (SAC) is vital for proper chromosome segregation during cell division and for maintaining genomic integrity; its disruption can cause aneuploidy and tumors. The BUB gene family ensures SAC fidelity by regulating kinetochore–microtubule attachments and mitotic progression. Dysregulation leads to chromosomal instability (CIN), contributing to cancer progression, heterogeneity, metastasis, and therapy resistance. Beyond mitosis, BUB proteins influence DNA repair, chromatin remodeling, transcription, and immune responses. They interact with cell cycle and genome stability pathways, impacting cancer prognosis and therapy response. Research is ongoing to validate BUB proteins as biomarkers and develop inhibitors, possibly combined with immunotherapies or DNA-damaging agents for resistant tumors. This review summarizes their functions, highlighting their potential in personalized cancer treatment.