PARP Pioneers: Using BRCA1/2 Mutation-targeted Inhibition to Revolutionize Breast Cancer Treatment.

IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY Current pharmaceutical design Pub Date : 2024-10-17 DOI:10.2174/0113816128322894241004051814
Navneet Sharma, Akash Bhati, Shagun Aggarwal, Kamal Shah, Hitesh Kumar Dewangan
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Abstract

Breast Cancer stands on the second position in the world in being common and women happen to have it with high rate of about five-folds around the world. The causes of occurrence can matter with different humans be it external factors or the internal genetic ones. Breast cancer is primarily driven by mutations in the BRCA1 and BRCA2 susceptibility genes. These BC susceptibility genes encode proteins critical for DNA homologous recombination repair (HRR). Poly (ADP ribose) polymerases (PARP) are the essential enzymes involved in the repairing of the damaged DNA. So the inhibition of these inhibitors can be considered as the promising strategy for targeting cancers with defective damage in the deoxyribonucleic acid. Olaparib and talazoparib are PARP inhibitors (PARPi) are being employed for the monotherapies in case of the deleterious germline HER2-negative and BRCA-mutated breast cancer. The potency of PARP for trapping on DNA and causes cytotoxicity may have difference in the safety and efficacy with the PARPi. The PARPi have been found its place in the all different types of Breast Cancers and have shown potential benefits. The purpose of this review is to provide an update on the oral poly(ADP-ribose) polymerase (PARP)inhibitors for the improvement in the treatment and management of Breast Cancer.

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PARP 先驱:利用 BRCA1/2 基因突变靶向抑制来革新乳腺癌治疗。
乳腺癌是世界上第二常见的癌症,全世界妇女患乳腺癌的比例高达五倍。乳腺癌的发病原因因人而异,既有外部因素,也有内在遗传因素。乳腺癌主要是由 BRCA1 和 BRCA2 易感基因突变引起的。这些 BC 易感基因编码对 DNA 同源重组修复(HRR)至关重要的蛋白质。聚(ADP 核糖)聚合酶(PARP)是参与修复受损 DNA 的重要酶。因此,抑制这些抑制剂可被视为针对脱氧核糖核酸缺陷性损伤的癌症的有效策略。奥拉帕利(Olaparib)和他拉唑帕利(talazoparib)是 PARP 抑制剂(PARPi),目前正被用于单药治疗有害的种系 HER2 阴性乳腺癌和 BRCA 突变乳腺癌。PARP 能捕获 DNA 并产生细胞毒性,这可能会影响 PARPi 的安全性和有效性。PARPi 已在各种不同类型的乳腺癌中找到了自己的位置,并显示出潜在的益处。本综述旨在提供有关口服聚(ADP-核糖)聚合酶(PARP)抑制剂的最新进展,以改善乳腺癌的治疗和管理。
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来源期刊
CiteScore
6.30
自引率
0.00%
发文量
302
审稿时长
2 months
期刊介绍: Current Pharmaceutical Design publishes timely in-depth reviews and research articles from leading pharmaceutical researchers in the field, covering all aspects of current research in rational drug design. Each issue is devoted to a single major therapeutic area guest edited by an acknowledged authority in the field. Each thematic issue of Current Pharmaceutical Design covers all subject areas of major importance to modern drug design including: medicinal chemistry, pharmacology, drug targets and disease mechanism.
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