PARP Inhibitors: Mechanism of Action
PARP Inhibitors: Mechanism of Action
复制标题
PARP 抑制剂：作用机制
DOI：
10.1007/978-981-16-4521-1_18
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Miki Yoshio
中科院分区：
文献类型：
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作者：
Sunada Shigeaki;Miki Yoshio
使用聚（ADP-核糖）聚合酶（PARP）抑制剂的合成致死疗法作为DNA修复功能降低的遗传性乳腺癌和卵巢癌（HBOC）的有效治疗方法继续引起关注，因为该治疗特别引起肿瘤的高敏感性。这种效应是由PARP诱导的DNA双链断裂（DSB）形成和同源重组（HR）修复功能缺陷的组合引起的，HR修复是DNA损伤的主要修复途径。另一方面，作为肿瘤异质性的肿瘤中的克隆进化引起合成致死途径的每个阶段的功能变化，导致出现对PARP抑制剂具有获得性抗性的癌细胞。获得性耐药性的各种分子机制已得到阐明。本章介绍了PARP抑制剂的合成致死机制、PARP抑制剂获得性耐药机制以及各种PARP抑制剂的发展。
Synthetic lethal therapy with poly(ADP-ribose) polymerase (PARP) inhibitors continues to attract attention as an effective treatment for hereditary breast and ovarian cancer (HBOC) with reduced DNA repair function because the treatment specifically causes high sensitivity in tumors. This effect is caused by the combination of PARP inhibitor-induced DNA double-strand break (DSB) formation and functional deficiency of homologous recombination (HR) repair, which is the main repair pathway for DNA damage. On the other hand, the clonal evolution in tumors as a tumor heterogeneity causes functional changes at each stage of the synthetic lethal pathway, resulting in the emergence of cancer cells with acquired resistance to PARP inhibitors. Various molecular mechanisms of the acquired resistance have been clarified. This chapter describes the synthetic lethal mechanism of PARP inhibitors, the mechanism of acquired resistance to PARP inhibitors, and the development of various PARP inhibitors.