摘要
尽管不同类型癌症患者的存活率有所提高,但抗肿瘤药物引起的心脏毒性仍然是一个关键问题。炭疽热治疗后心功能不全Ines在历史上一直是一个主要问题。然而,靶向治疗和生物分子也可以诱发可逆和不可逆转的心功能不全。在过去的几年里,癌症免疫类人猿已进化为临床治疗范围广泛的固体和造血恶性肿瘤,先前被赋予了不良的预后。免疫检查点抑制剂是最前沿的免疫治疗:细胞毒性T淋巴细胞相关抗原4(CTLA-4)和程序性细胞死亡1(Pd-1)及其配体Pd-L1的靶向作用。ipilimumab(抗CTLA-4)iS是检查点抑制剂的教父,而针对pd-1(nivolumab和pbrobrolizumab)和pd-l1(atezolizumab、durvalumab、avelumab和bms-946559)的几种阻断单克隆抗体则是他们的教父。e已开发。CTLA-4和Pd-1/Pd-L1通路抑制剂可释放抗肿瘤免疫,介导肿瘤消退。虽然ctla-4抑制剂和pd-1和pd-l1阻断剂是常见的。Ly与广泛的免疫相关不良事件有关,心脏毒性一直被低估.然而,早期的动物研究已经证明,在ctla-4抑制和pd-1 del之后。可发生自身免疫性心肌炎。此外,PD-1和PD-L1可在鼠和人心肌细胞中表达.在过去的几年里,有几例致命心力衰竭的病例被记录在案。黑色素瘤患者用检查点抑制剂治疗。最近与检查点抑制剂有关的心血管毒性效应的经验介绍了重要的生物和clin概念。与未来的肿瘤学试验和临床实践密切相关。
关键词: 癌症,心脏毒性,检查点,CTLA-4,黑色素瘤,心肌炎,PD-1,PD-L1。
Current Medicinal Chemistry
Title:Immune Checkpoint Inhibitors and Cardiac Toxicity: An Emerging Issue
Volume: 25 Issue: 11
关键词: 癌症,心脏毒性,检查点,CTLA-4,黑色素瘤,心肌炎,PD-1,PD-L1。
摘要: Although survival of patients with different types of cancer has improved, cardiotoxicity induced by anti-neoplastic drugs remains a critical issue. Cardiac dysfunction after treatment with anthracyclines has historically been a major problem. However, also targeted therapies and biological molecules can induce reversible and irreversible cardiac dysfunction. Over the last years, cancer immunotherapies haverevolutionized the clinical management of a wide spectrum of solid and hematopoietic malignancies previously endowed with poor prognosis. Immune checkpoint inhibitors are at the forefront of immunotherapy: the two most prominent are the targeting of cytotoxic-T-lymphocyte-associated antigen 4 (CTLA- 4) and of programmed cell death 1 (PD-1) and its ligand PD-L1. Ipilimumab (anti-CTLA-4) is the godfather of checkpoint inhibitors, whereas several blocking monoclonal antibodies targeting PD-1 (nivolumab and pembrolizumab) and PD-L1 (atezolizumab, durvalumab, avelumab, and BMS-946559) have been developed. Inhibitors of CTLA-4 and PD-1/PD-L1 pathway can unleash anti-tumor immunity and mediate cancer regressions. Although CTLA-4 inhibitors and PD-1 and PD-L1 blocking agents are frequently associated with a wide spectrum of immune-related adverse events, cardiac toxicity has been underestimated. However, early animal studies have demonstrated that after CTLA-4 inhibition and PD-1 deletion autoimmune myocarditis can occur. Moreover, PD-1 and PD-L1 can be expressed in rodent and human cardiomyocytes. During the last years several cases of fatal heart failure have been documented in melanoma patients treated with checkpoint inhibitors. The recent experience with cardiovascular toxic effects associated with checkpoint inhibitors introduces important concepts biologically and clinically relevant for future oncology trials and clinical practice.
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Cite this article as:
Immune Checkpoint Inhibitors and Cardiac Toxicity: An Emerging Issue, Current Medicinal Chemistry 2018; 25 (11) . https://dx.doi.org/10.2174/0929867324666170407125017
DOI https://dx.doi.org/10.2174/0929867324666170407125017 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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