Department of Medical Oncology, Cancer Hospital, National Cancer Center, National Clinical Research Center for Cancer, Chinese Academy of Medical Sciences and Peking Union Medical College, Chaoyang District, Pan jia yuan nan Road 17, Beijing, 100021, China.
J Transl Med. 2024 Aug 5;22(1):739. doi: 10.1186/s12967-024-05537-5.
In recent years, with advancements in medicine, the survival period of patients with tumours has significantly increased. The adverse effects of tumour treatment on patients, especially cardiac toxicity, have become increasingly prominent. In elderly patients with breast cancer, treatment-related cardiovascular toxicity has surpassed cancer itself as the leading cause of death. Moreover, in recent years, an increasing number of novel antitumour drugs, such as multitargeted agents, antibody‒drug conjugates (ADCs), and immunotherapies, have been applied in clinical practice. The cardiotoxicity induced by these drugs has become more pronounced, leading to a complex and diverse mechanism of cardiac damage. The risks of unintended cardiovascular toxicity are increased by high-dose anthracyclines, immunotherapies, and concurrent radiation, in addition to traditional cardiovascular risk factors such as smoking, hypertension, diabetes, hyperlipidaemia, and obesity. However, these factors do not fully explain why only a subset of individuals experience treatment-related cardiac toxicity, whereas others with similar clinical features do not. Recent studies indicate that genetics play a significant role in susceptibility to the development of cardiovascular toxicity from cancer therapies. These genes are involved in drug metabolism, oxidative damage, cardiac dysfunction, and other processes. Moreover, emerging evidence suggests that epigenetics also plays a role in drug-induced cardiovascular toxicity. We conducted a review focusing on breast cancer as an example to help oncologists and cardiologists better understand the mechanisms and effects of genetic factors on cardiac toxicity. In this review, we specifically address the relationship between genetic alterations and cardiac toxicity, including chemotherapy-related genetic changes, targeted therapy-related genetic changes, and immune therapy-related genetic changes. We also discuss the role of epigenetic factors in cardiac toxicity. We hope that this review will improve the risk stratification of patients and enable therapeutic interventions that mitigate these unintended adverse consequences of life-saving cancer treatments.
近年来，随着医学的进步，肿瘤患者的生存期显著延长。肿瘤治疗对患者的不良影响，尤其是心脏毒性，变得越来越突出。在老年乳腺癌患者中，与治疗相关的心血管毒性已超过癌症本身，成为死亡的主要原因。此外，近年来，越来越多的新型抗肿瘤药物，如多靶点药物、抗体药物偶联物（ADC）和免疫疗法，已应用于临床实践。这些药物引起的心脏毒性变得更加明显，导致心脏损伤的机制变得复杂多样。高剂量蒽环类药物、免疫疗法和同步放疗，以及吸烟、高血压、糖尿病、高脂血症和肥胖等传统心血管危险因素，增加了意外心血管毒性的风险。然而，这些因素并不能完全解释为什么只有一部分人会经历与治疗相关的心脏毒性，而其他具有相似临床特征的人则不会。最近的研究表明，遗传因素在癌症治疗相关心血管毒性的易感性中起着重要作用。这些基因参与药物代谢、氧化损伤、心脏功能障碍和其他过程。此外，新出现的证据表明，表观遗传学也在药物引起的心血管毒性中发挥作用。我们进行了一项以乳腺癌为例的综述，以帮助肿瘤学家和心脏病学家更好地理解遗传因素对心脏毒性的机制和影响。在这篇综述中，我们特别关注了基因改变与心脏毒性之间的关系，包括化疗相关的基因改变、靶向治疗相关的基因改变和免疫治疗相关的基因改变。我们还讨论了表观遗传因素在心脏毒性中的作用。我们希望这篇综述能改善患者的风险分层，并能进行治疗干预，减轻这些挽救生命的癌症治疗的意外不良后果。
