PARP 抑制剂耐药性的分子机制。

Oncoscience Pub Date : 2024-09-23 eCollection Date: 2024-01-01 DOI:10.18632/oncoscience.610
Yi Huang, Simin Chen, Nan Yao, Shikai Lin, Junyi Zhang, Chengrui Xu, Chenxuan Wu, Guo Chen, Danyang Zhou
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摘要

聚(ADP-核糖)聚合酶(PARP)抑制剂(PARPi)是第一种获批的利用合成致死性的抗癌药物。PARPi 可选择性地杀死存在同源重组修复缺陷(HRD)的癌细胞,因此被广泛用于治疗 BRCA1/2 突变的卵巢癌、乳腺癌、胰腺癌和前列腺癌。目前,包括奥拉帕利(Olaparib)、鲁卡帕利(Rucaparib)、尼拉帕利(Niraparib)和塔拉唑帕利(Talazoparib)在内的四种 PARPi 已被开发出来,大大改善了癌症患者的临床疗效。然而,越来越多的证据表明,出现了所需的或新的耐药性。在本综述中,我们将讨论导致 PARPi 耐药的分子机制,并综述克服 PARPi 耐药的潜在策略。
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Molecular mechanism of PARP inhibitor resistance.

Poly (ADP-ribose) polymerases (PARP) inhibitors (PARPi) are the first-approved anticancer drug designed to exploit synthetic lethality. PARPi selectively kill cancer cells with homologous recombination repair deficiency (HRD), as a result, PARPi are widely employed to treated BRCA1/2-mutant ovarian, breast, pancreatic and prostate cancers. Currently, four PARPi including Olaparib, Rucaparib, Niraparib, and Talazoparib have been developed and greatly improved clinical outcomes in cancer patients. However, accumulating evidences suggest that required or de novo resistance emerged. In this review, we discuss the molecular mechanisms leading to PARPi resistances and review the potential strategies to overcome PARPi resistance.

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