DNA replication machinery of tumor cell

DNA replication machinery in tumor cells comprises a network of proteins and multi-protein complexes that coordinate the initiation, elongation, and completion of DNA synthesis during the cell cycle, with regulated activity mainly in the S-phase. In cancer, this machinery is often dysregulated, due to mutations in oncogenes or tumor suppressors such as Rb, p16, CDK4/6, and DNA repair genes like BRCA1/2, resulting in uncontrolled proliferation and genomic instability. The replication machinery presents numerous actionable targets for anticancer therapy, including enzymes required for DNA synthesis and cell cycle progression, with many current therapies directed at inhibiting or degrading these components or interfering with their pathways. Monitoring biomarkers such as Ki-67 and γH2AX can provide information about the replication status and DNA damage, important for both patient selection and treatment efficacy assessment. Despite efficacy, targeting DNA replication machinery poses safety risks including toxicity to normal dividing cells and resistance development

Other names

DNA synthesis machinery in tumor cellscell cycle DNA replication apparatusreplication complex in cancer

Inhibition of DNA replication enzymes (blockage of DNA polymerase or helicase activity) Disruption of nucleotide metabolism Induction of replication stress and DNA damage Targeted degradation of regulatory proteins (via PROTACs)