Deleted Journal, Год журнала: 2025, Номер unknown, С. 1 - 13
Опубликована: Март 31, 2025
Cells have evolved a sophisticated network of biological pathways, collectively termed the DNA damage response (DDR), to coordinate repair, cell cycle checkpoint activation, and other cellular responses, thereby preventing inheritance harmful mutations. Genes encoding DDR factors are frequently mutated in cancer, leading genomic instability promoting tumorigenesis. However, these mutations also create vulnerabilities that can be exploited for cancer therapy using DNA-damaging cytotoxic drugs radiotherapy. Advances our understanding targeting illuminated its impact on therapeutic exemplified by tumors with breast suppressor gene 1/2 (BRCA1/2) Impaired homologous recombination repair forces reliance alternative mechanisms, rendering them susceptible poly ADP-ribose polymerase (PARP) inhibitors. These inhibitors selectively eliminate cells deficiencies, serving as paradigm targeted therapy. Moreover, numerous synthetic lethal relationships between genes been identified. Consequently, DDR-targeted therapies offer potential enhance efficacy radiotherapy chemotherapy clinical treatment. This review discusses latest small-molecule inhibitors, particular focus those currently undergoing evaluation.
Язык: Английский