Piscone Anna, Gorini Francesca, Ambrosio Susanna, Noviello Anna, Scala Giovanni, Majello Barbara, Amente Stefano
Department of Molecular Medicine and Medical Biotechnologies, University of Naples 'Federico II', 80131 Naples, Italy.
Department of Biology, University of Naples 'Federico II', 80138 Naples, Italy.
Cells. 2025 Jan 14;14(2):112. doi: 10.3390/cells14020112.
Genomic integrity is critical for cellular homeostasis, preventing the accumulation of mutations that can drive diseases such as cancer. Among the mechanisms safeguarding genomic stability, the Base Excision Repair (BER) pathway plays a pivotal role in counteracting oxidative DNA damage caused by reactive oxygen species. Central to this pathway are enzymes like 8-oxoguanine glycosylase 1 (OGG1), which recognize and excise 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) lesions, thereby initiating a series of repair processes that restore DNA integrity. BER inhibitors have recently been identified as a promising approach in cancer therapy, increasing the sensitivity of cancer cells to radiotherapy and chemotherapy. By exploiting tumor-specific DNA repair dependencies and synthetic lethal interactions, these inhibitors could be used to selectively target cancer cells while sparing normal cells. This review provides a robust reference for scientific researchers, offering an updated perspective on small-molecule inhibitors targeting the 8-oxodG-BER pathway and highlighting their potential role in expanding cancer treatment strategies.
基因组完整性对于细胞稳态至关重要，可防止驱动癌症等疾病的突变积累。在维护基因组稳定性的机制中，碱基切除修复（BER）途径在对抗由活性氧引起的氧化性DNA损伤方面发挥着关键作用。该途径的核心是诸如8-氧鸟嘌呤糖基化酶1（OGG1）之类的酶，它们识别并切除8-氧代-7,8-二氢-2'-脱氧鸟苷（8-氧代脱氧鸟苷，8-oxodG）损伤，从而启动一系列修复过程以恢复DNA完整性。BER抑制剂最近已被确定为癌症治疗中的一种有前景的方法，可提高癌细胞对放疗和化疗的敏感性。通过利用肿瘤特异性DNA修复依赖性和合成致死相互作用，这些抑制剂可用于选择性地靶向癌细胞，同时使正常细胞免受影响。本综述为科研人员提供了有力的参考，提供了针对8-oxodG-BER途径的小分子抑制剂的最新观点，并强调了它们在扩展癌症治疗策略中的潜在作用。
