Intercellular pathways of cancer treatment-related cardiotoxicity and their therapeutic implications: the paradigm of radiotherapy

IF 12 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Stella Logotheti , Athanasia Pavlopoulou , Hamid Khoshfekr Rudsari , Anne-Marie Galow , Yağmur Kafalı , Efthymios Kyrodimos , Aris I. Giotakis , Stephan Marquardt , Anastasia Velalopoulou , Ioannis I. Verginadis , Constantinos Koumenis , Thorsten Stiewe , Jerome Zoidakis , Ilangko Balasingham , Robert David , Alexandros G. Georgakilas
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引用次数: 0

Abstract

Advances in cancer therapeutics have improved patient survival rates. However, cancer survivors may suffer from adverse events either at the time of therapy or later in life. Cardiovascular diseases (CVD) represent a clinically important, but mechanistically understudied complication, which interfere with the continuation of best-possible care, induce life-threatening risks, and/or lead to long-term morbidity. These concerns are exacerbated by the fact that targeted therapies and immunotherapies are frequently combined with radiotherapy, which induces durable inflammatory and immunogenic responses, thereby providing a fertile ground for the development of CVDs. Stressed and dying irradiated cells produce ‘danger’ signals including, but not limited to, major histocompatibility complexes, cell-adhesion molecules, proinflammatory cytokines, and damage-associated molecular patterns. These factors activate intercellular signaling pathways which have potentially detrimental effects on the heart tissue homeostasis. Herein, we present the clinical crosstalk between cancer and heart diseases, describe how it is potentiated by cancer therapies, and highlight the multifactorial nature of the underlying mechanisms. We particularly focus on radiotherapy, as a case known to often induce cardiovascular complications even decades after treatment. We provide evidence that the secretome of irradiated tumors entails factors that exert systemic, remote effects on the cardiac tissue, potentially predisposing it to CVDs. We suggest how diverse disciplines can utilize pertinent state-of-the-art methods in feasible experimental workflows, to shed light on the molecular mechanisms of radiotherapy-related cardiotoxicity at the organismal level and untangle the desirable immunogenic properties of cancer therapies from their detrimental effects on heart tissue. Results of such highly collaborative efforts hold promise to be translated to next-generation regimens that maximize tumor control, minimize cardiovascular complications, and support quality of life in cancer survivors.

癌症治疗相关心脏毒性的细胞间途径及其治疗意义:放射治疗范例。
癌症疗法的进步提高了患者的生存率。然而,癌症幸存者可能在接受治疗时或之后的生活中遭受不良事件的影响。心血管疾病(CVD)是临床上重要的并发症之一,但其机理研究不足,影响了最佳治疗的继续,诱发危及生命的风险,和/或导致长期发病。靶向疗法和免疫疗法经常与放疗结合使用,而放疗会诱发持久的炎症和免疫原性反应,从而为心血管疾病(CVDs)的发生提供了肥沃的土壤,这加剧了人们的担忧。受压和濒死的辐照细胞会产生 "危险 "信号,包括但不限于主要组织相容性复合物、细胞粘附分子、促炎细胞因子和损伤相关分子模式。这些因素会激活细胞间信号通路,从而对心脏组织的平衡产生潜在的有害影响。在此,我们将介绍癌症与心脏疾病之间的临床串扰,描述癌症疗法如何增强这种串扰,并强调其潜在机制的多因素性质。我们尤其关注放疗,因为众所周知,放疗往往会诱发心血管并发症,甚至在治疗后数十年也是如此。我们提供的证据表明,辐照肿瘤的分泌组包含对心脏组织产生系统性、远距离影响的因子,有可能使心脏组织易患心血管疾病。我们建议不同学科如何在可行的实验工作流程中利用相关的先进方法,在机体水平上阐明放疗相关心脏毒性的分子机制,并将癌症疗法的理想免疫原性与其对心脏组织的有害影响区分开来。这些高度合作的成果有望转化为下一代治疗方案,从而最大限度地控制肿瘤,减少心血管并发症,提高癌症幸存者的生活质量。
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来源期刊
CiteScore
23.00
自引率
0.70%
发文量
222
审稿时长
90 days
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.
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