癌症靶向DNA损伤修复精准医疗策略

IF 4 3区医学 Q1 PHARMACOLOGY & PHARMACY

Current Opinion in Pharmacology Pub Date : 2023-06-01 DOI:10.1016/j.coph.2023.102381

Juliette Brownlie , Sanat Kulkarni , Mashael Algethami , Jennie N. Jeyapalan , Nigel P. Mongan , Emad A. Rakha , Srinivasan Madhusudan

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引用次数: 2

摘要

DNA修复靶向治疗是癌症的一种很有前途的精准治疗策略。PARP抑制剂的开发和临床应用改变了许多BRCA种系缺陷型乳腺癌和卵巢癌症以及铂敏感上皮性卵巢癌患者的生活。然而，从PARP抑制剂的临床使用中吸取的经验教训也证实，并非所有患者都因固有或获得性耐药性而有反应。因此，寻找额外的合成杀伤方法是转化和临床研究的一个活跃领域。在此，我们回顾了PARP抑制剂和其他进化的DNA修复靶点的当前临床状态，包括ATM、ATR、WEE1抑制剂和癌症中的其他。

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Targeting DNA damage repair precision medicine strategies in cancer

DNA repair targeted therapeutics is a promising precision medicine strategy in cancer. The development and clinical use of PARP inhibitors has transformed lives for many patients with BRCA germline deficient breast and ovarian cancer as well as platinum sensitive epithelial ovarian cancers. However, lessons learnt from the clinical use of PARP inhibitors also confirm that not all patients respond either due to intrinsic or acquired resistance. Therefore, the search for additional synthetic lethality approaches is an active area of translational and clinical research. Here, we review the current clinical state of PARP inhibitors and other evolving DNA repair targets including ATM, ATR, WEE1 inhibitors and others in cancer.

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来源期刊

Current Opinion in Pharmacology 医学-药学

CiteScore

8.80

自引率

2.50%

发文量

131

审稿时长

4-8 weeks

期刊介绍： Current Opinion in Pharmacology (COPHAR) publishes authoritative, comprehensive, and systematic reviews. COPHAR helps specialists keep up to date with a clear and readable synthesis on current advances in pharmacology and drug discovery. Expert authors annotate the most interesting papers from the expanding volume of information published today, saving valuable time and giving the reader insight on areas of importance.