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General Review Article

PARP抑制剂治疗卵巢癌的研究进展及其耐药机制

卷 21, 期 2, 2020

页: [167 - 178] 页: 12

弟呕挨: 10.2174/1389450120666190925123507

价格: $65

摘要

晚期卵巢癌的标准治疗方法是细胞减灭术，然后进行细胞毒性化学疗法。但是，它具有高复发风险和不良预后。聚（ADPribose）聚合酶（PARP）抑制剂选择性地靶向无法修复的肿瘤细胞中的DNA双链断裂（DSB），并诱导BRCA1 / 2突变癌症的合成致死性。 PARP抑制剂在临床上用于治疗复发性卵巢癌，并且在具有同源重组修复（HRR）途径缺陷的卵巢癌患者中显示出显着的疗效。对于没有HR缺陷的患者，PARP抑制剂也具有显着的临床益处。随着PARP抑制剂在临床上的广泛应用，获得耐药性的可能性很高。因此，应采用临床策略来控制PARP抑制剂的耐药性。这项研究旨在总结PARP抑制剂的适应症和毒性，作用机理，耐药性的靶向治疗以及治疗耐药性疾病的潜在方法。我们使用术语“卵巢癌”和每种PARP抑制剂的名称作为关键字来搜索Pubmed上医学主题词（MeSH）上发表的文章，并使用关键字“ clinicaltrials.gov”和“ google.com/patents”作为关键字。 FDA已批准olaparib，niraparib和rucaparib用于治疗复发性上皮性卵巢癌（EOC）。 Talazoparib和veliparib目前处于早期试验中，并显示出令人鼓舞的临床结果。对PARP抑制剂产生抗药性的机制及其克服策略仍不清楚。了解对PARP抑制剂的抗药性机制及其与铂抗药性的关系，可能有助于抗药性疗法的发展以及在未来卵巢癌临床治疗中优化药物应用顺序。

关键词: PARP抑制剂，卵巢癌，靶向治疗，毒性，耐药机制，MeSH。

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图形摘要

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