Olaparib: A Chemosensitizer for the Treatment of Glioblastoma.

IF 3.3 3区 医学 Q2 CHEMISTRY, MEDICINAL Mini reviews in medicinal chemistry Pub Date : 2024-10-23 DOI:10.2174/0113895575318854241014101928
Naresh Dhanavath, Priya Bisht, Mohini Santosh Jamadade, Krishna Murti, Pranay Wal, Nitesh Kumar
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Abstract

Glioblastoma (GBM) is the most prevalent and deadly primary brain tumor. The current treatment for GBM includes adjuvant chemotherapy with temozolomide (TMZ), radiation therapy, and surgical tumor excision. There is still an issue because 50% of patients with GBM who get TMZ have low survival rates due to TMZ resistance. The activation of several DNA repair mechanisms, such as Base Excision Repair (BER), DNA Mismatch Repair (MMR), and O-6- Methylguanine-DNA Methyltransferase (MGMT), is the main mechanism via which TMZ resistance develops. The zinc-finger DNA-binding enzyme poly (ADP-ribose) polymerase-1 (PARP1), which is activated by binding to DNA breaks, affects the activation of the MGMT, BER, and MMR pathway deficiency, which results in TMZ resistance in GBM. PARP inhibitors have been studied recently as sensitizing medications to increase TMZ potency. The first member of the PARP inhibitor family to be identified was Olaparib. It inhibits PARP1 and PARP2, which causes apoptosis in cancer cells and DNA strand break. Olaparib is currently investigated as a radio- and/or chemo-sensitizer in addition to being used as a single agent because it may increase the cytotoxic effects of other treatments. This review addresses Olaparib and its significance in treating TMZ resistance in GBM.

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奥拉帕利治疗胶质母细胞瘤的化疗增敏剂。
胶质母细胞瘤(GBM)是最常见、最致命的原发性脑肿瘤。目前治疗 GBM 的方法包括替莫唑胺(TMZ)辅助化疗、放射治疗和手术切除肿瘤。但仍存在一个问题,即50%接受替莫唑胺治疗的GBM患者因对替莫唑胺产生耐药性而导致生存率低下。碱基切除修复(BER)、DNA 错配修复(MMR)和 O-6- 甲基鸟嘌呤-DNA 甲基转移酶(MGMT)等 DNA 修复机制的激活是 TMZ 产生耐药性的主要机制。锌指DNA结合酶多(ADP-核糖)聚合酶-1(PARP1)通过与DNA断裂结合而被激活,影响MGMT、BER和MMR途径缺陷的激活,从而导致GBM的TMZ耐药。最近研究发现,PARP 抑制剂可作为增敏药物提高 TMZ 的效力。第一个被发现的 PARP 抑制剂家族成员是 Olaparib。它能抑制 PARP1 和 PARP2,从而导致癌细胞凋亡和 DNA 链断裂。除了作为单药使用外,奥拉帕利目前还被研究用作放射和/或化疗增敏剂,因为它可以增强其他治疗方法的细胞毒性作用。本综述探讨了奥拉帕利及其在治疗 GBM 中 TMZ 耐药性方面的意义。
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来源期刊
CiteScore
7.80
自引率
0.00%
发文量
231
审稿时长
6 months
期刊介绍: The aim of Mini-Reviews in Medicinal Chemistry is to publish short reviews on the important recent developments in medicinal chemistry and allied disciplines. Mini-Reviews in Medicinal Chemistry covers all areas of medicinal chemistry including developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, drug targets, and natural product research and structure-activity relationship studies. Mini-Reviews in Medicinal Chemistry is an essential journal for every medicinal and pharmaceutical chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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