{"title":"Cisplatin in the era of PARP inhibitors and immunotherapy","authors":"Mingrui Duan , Shuguang Leng , Peng Mao","doi":"10.1016/j.pharmthera.2024.108642","DOIUrl":null,"url":null,"abstract":"<div><p>Platinum compounds such as cisplatin, carboplatin and oxaliplatin are widely used in chemotherapy. Cisplatin induces cytotoxic DNA damage that blocks DNA replication and gene transcription, leading to arrest of cell proliferation. Although platinum therapy alone is effective against many tumors, cancer cells can adapt to the treatment and gain resistance. The mechanisms for cisplatin resistance are complex, including low DNA damage formation, high DNA repair capacity, changes in apoptosis signaling pathways, rewired cell metabolisms, and others. Drug resistance compromises the clinical efficacy and calls for new strategies by combining cisplatin with other therapies. Exciting progress in cancer treatment, particularly development of poly (ADP-ribose) polymerase (PARP) inhibitors and immune checkpoint inhibitors, opened a new chapter to combine cisplatin with these new cancer therapies. In this Review, we discuss how platinum synergizes with PARP inhibitors and immunotherapy to bring new hope to cancer patients.</p></div>","PeriodicalId":402,"journal":{"name":"Pharmacology & Therapeutics","volume":"258 ","pages":"Article 108642"},"PeriodicalIF":12.0000,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pharmacology & Therapeutics","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0163725824000627","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Platinum compounds such as cisplatin, carboplatin and oxaliplatin are widely used in chemotherapy. Cisplatin induces cytotoxic DNA damage that blocks DNA replication and gene transcription, leading to arrest of cell proliferation. Although platinum therapy alone is effective against many tumors, cancer cells can adapt to the treatment and gain resistance. The mechanisms for cisplatin resistance are complex, including low DNA damage formation, high DNA repair capacity, changes in apoptosis signaling pathways, rewired cell metabolisms, and others. Drug resistance compromises the clinical efficacy and calls for new strategies by combining cisplatin with other therapies. Exciting progress in cancer treatment, particularly development of poly (ADP-ribose) polymerase (PARP) inhibitors and immune checkpoint inhibitors, opened a new chapter to combine cisplatin with these new cancer therapies. In this Review, we discuss how platinum synergizes with PARP inhibitors and immunotherapy to bring new hope to cancer patients.
顺铂、卡铂和奥沙利铂等铂化合物被广泛用于化疗。顺铂可诱导细胞毒性 DNA 损伤,从而阻止 DNA 复制和基因转录,导致细胞增殖停止。虽然单独使用铂类药物治疗对许多肿瘤有效,但癌细胞会适应这种治疗方法并产生抗药性。顺铂产生耐药性的机制十分复杂,包括 DNA 损伤形成低、DNA 修复能力强、凋亡信号通路发生变化、细胞代谢重新连接等。耐药性损害了临床疗效,因此需要将顺铂与其他疗法相结合的新策略。癌症治疗领域取得了令人振奋的进展,尤其是多(ADP-核糖)聚合酶(PARP)抑制剂和免疫检查点抑制剂的开发,为顺铂与这些新型癌症疗法的结合揭开了新的篇章。在本综述中,我们将讨论铂如何与 PARP 抑制剂和免疫疗法协同作用,为癌症患者带来新的希望。
期刊介绍:
Pharmacology & Therapeutics, in its 20th year, delivers lucid, critical, and authoritative reviews on current pharmacological topics.Articles, commissioned by the editor, follow specific author instructions.This journal maintains its scientific excellence and ranks among the top 10 most cited journals in pharmacology.