a Laboratory of Thrombosis, Haemostasis and Valvular Heart Diseases, GIGA-Cardiovascular Sciences, Department of Cardiology , University of Liège, CHU Liège , Liège , Belgium.
b Gruppo Villa Maria Care and Research , Anthea Hospital , Bari , Italy.
Expert Opin Pharmacother. 2018 Apr;19(5):431-442. doi: 10.1080/14656566.2018.1446080. Epub 2018 Mar 1.
Available data indicate that survivors of breast cancer and Hodgkin lymphoma who received mediastinal radiotherapy are at increased risk of developing radiation-induced cardiovascular diseases (RICVD) one or two decades after treatment. Although the risk with modern radiation treatment is likely to be lower in these patient groups, cardiotoxicity is still observed in a subset of patients. In addition, radiation-associated cardiovascular complications can, in the future, extend to other groups of cancer patients who are treated for tumors that are localized near the heart.
The authors briefly describe the most commonly observed types of RICVD. They then present an overview of preclinical animal and cellular models that have been used to investigate the mechanisms underlying RICVD pathophysiology. The beneficial effects of available drugs, and potential targets for new molecules are also reported.
There is a need to develop cardio-oncological programs and pharmacotherapies specifically targeting RICVD. Beyond statins, ACE inhibitors, anti-inflammatory and antioxidant agents, preclinical studies indicate that TGFβ receptor I inhibitors, Sestrin2 inducers, recombinant neuregulin-1 and miR-21 inhibitors might represent novel promising strategies. In order to properly determine the optimal therapeutic index for these molecules, in vivo models combining cancer and RICVD should be envisioned.
现有数据表明,乳腺癌和霍奇金淋巴瘤幸存者在接受纵隔放疗后一到二十年,发生放射性心血管疾病(RICVD)的风险增加。尽管这些患者群体接受现代放射治疗的风险可能较低,但仍有一部分患者会出现心脏毒性。此外,未来与放射相关的心血管并发症可能会扩展到其他接受心脏附近肿瘤治疗的癌症患者群体。
作者简要描述了最常见的 RICVD 类型。然后,他们介绍了用于研究 RICVD 病理生理学机制的临床前动物和细胞模型的概述。还报告了现有药物的有益作用以及新分子的潜在靶点。
需要开发专门针对 RICVD 的心脏肿瘤学计划和药物治疗。除了他汀类药物、ACE 抑制剂、抗炎和抗氧化剂外,临床前研究表明,TGFβ受体 I 抑制剂、Sestrin2 诱导剂、重组神经调节素-1 和 miR-21 抑制剂可能代表新的有前途的策略。为了正确确定这些分子的最佳治疗指数,应设想结合癌症和 RICVD 的体内模型。