| PARP抑制剂耐药机理的研究进展 |
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| 引用本文： | 杨馥珺,冯笑山. PARP抑制剂耐药机理的研究进展[J]. 现代肿瘤医学, 2022, 0(10): 1894-1897. DOI: 10.3969/j.issn.1672-4992.2022.10.037 |
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| 作者姓名： | 杨馥珺 冯笑山 |
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| 作者单位： | 河南科技大学临床医学院,河南科技大学第一附属医院,河南 洛阳 471003 |
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| 摘 要： | 聚ADP-核糖聚合酶（Poly ADP-ribose polymerase,PARP）抑制剂（PARPi）是一组靶向携带BRCA1/2或其他同源重组因子有害突变的乳腺癌与卵巢癌的新型抗癌药物。 PARPi的临床应用已取得显著成果,是近年来临床肿瘤学的重大突破之一。然而,PARPi耐药正在成为一个严重的临床问题。研究和了解PARPi耐药机理对克服肿瘤耐药和提高疗效具有重要意义。最近的研究进展已经揭示了一些诱发PARPi耐药的机制,包括上调多药耐药基因,改变PARylation酶,重建同源重组修复和恢复复制叉稳定性。本文将综述这些变化如何导致癌细胞对PARPi产生耐药并讨论克服PARPi耐药的可能策略。
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| 关 键 词： | PARP抑制剂 耐药 乳腺癌 卵巢癌 BRCA DNA损伤修复 |
Advances in the mechanisms of PARP inhibitor resistance |
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| YANG Fujun,FENG Xiaoshan. Advances in the mechanisms of PARP inhibitor resistance[J]. Journal of Modern Oncology, 2022, 0(10): 1894-1897. DOI: 10.3969/j.issn.1672-4992.2022.10.037 |
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| Authors: | YANG Fujun FENG Xiaoshan |
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| Affiliation: | The First Affiliated Hospital,College of Clinical Medicine of Henan University of Science and Technology,Henan Luoyang 471003,China. |
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| Abstract: | Poly ADP-ribose polymerase (PARP) inhibitors (PARPi) is a group of novel anticancer agents targeting breast and ovarian cancers with disruptive mutations in BRCA1/2 or other homologue recombination (HR) factors.Clinical application of PARPi has achieved significant outcomes,which is one of the major breakthroughs in clinical oncology in recent years. However,PARPi resistance is emerging as a major clinical problem.Investigation and understanding the mechanisms of PARPi resistance is of pivotal significance for overcoming the potential resistance and improving the therapeutic efficacy.Recent advances have identified a few mechanisms that contribute to PARPi resistance,including upregulation of multidrug resistant genes,modification of PARylation enzymes,restoration of homologous recombination repair and/or stabilization of the replication forks.This review will discuss how these changes render the cancer cells resistant to PARPi and the potential strategies that may be used to overcome the resistance. |
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| Keywords: | PARP inhibitor drug resistance breast cancer ovarian cancer BRCA DNA damage and repair |
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