DNA Damage by Radiopharmaceuticals and Mechanisms of Cellular Repair.
DNA Damage by Radiopharmaceuticals and Mechanisms of Cellular Repair.
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DOI：
10.3390/pharmaceutics15122761
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发表时间：
2023-12-12
期刊：
影响因子：
5.4
通讯作者：
Esfahani SA
中科院分区：
文献类型：
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作者：
Khazaei Monfared Y;Heidari P;Klempner SJ;Mahmood U;Parikh AR;Hong TS;Strickland MR;Esfahani SA
DNA是一种有机分子，极易受到内部和外部因素引起的化学变化和断裂的影响。细胞具有复杂和先进的机制，包括DNA修复，损伤耐受，细胞周期检查点和细胞死亡途径，它们共同最大限度地减少了DNA损伤的潜在有害影响。然而，在癌细胞中，正常的DNA损伤耐受性和反应过程被破坏或失调。这导致癌细胞内的诱变和基因组不稳定性增加，这是癌症进展和治疗抗性的已知驱动因素。另一方面，在快速分裂的癌细胞中，基因组的固有不稳定性可以被利用作为一种工具，通过用放射性药物破坏DNA来杀死癌细胞。随着靶向放射性药物治疗（RPT）领域在肿瘤学中的迅速发展，深入了解放射性药物对肿瘤和健康组织DNA的全身辐射传递的影响至关重要。由RPT引起的DNA损伤和修复途径的分布和激活可以基于放射性同位素和分子靶的特征而不同。在这里，我们提供了一个全面的讨论RPTs的生物学效应，主要集中在不同的放射性同位素在诱导直接和间接的DNA损伤和激活DNA修复途径的作用。
DNA is an organic molecule that is highly vulnerable to chemical alterations and breaks caused by both internal and external factors. Cells possess complex and advanced mechanisms, including DNA repair, damage tolerance, cell cycle checkpoints, and cell death pathways, which together minimize the potentially harmful effects of DNA damage. However, in cancer cells, the normal DNA damage tolerance and response processes are disrupted or deregulated. This results in increased mutagenesis and genomic instability within the cancer cells, a known driver of cancer progression and therapeutic resistance. On the other hand, the inherent instability of the genome in rapidly dividing cancer cells can be exploited as a tool to kill by imposing DNA damage with radiopharmaceuticals. As the field of targeted radiopharmaceutical therapy (RPT) is rapidly growing in oncology, it is crucial to have a deep understanding of the impact of systemic radiation delivery by radiopharmaceuticals on the DNA of tumors and healthy tissues. The distribution and activation of DNA damage and repair pathways caused by RPT can be different based on the characteristics of the radioisotope and molecular target. Here we provide a comprehensive discussion of the biological effects of RPTs, with the main focus on the role of varying radioisotopes in inducing direct and indirect DNA damage and activating DNA repair pathways.
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影响因子：
2.6
作者：
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影响因子：
10.4
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影响因子：
3.9
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影响因子：
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