Hara Akiyoshi
Department of Clinical Pharmacotherapeutics, Tohoku Medical and Pharmaceutical University.
Yakugaku Zasshi. 2025;145(2):121-132. doi: 10.1248/yakushi.24-00185.
Many anticancer drugs, including anthracycline drugs, pose a risk of cardiovascular damage as an adverse reaction. This can detrimentally impact the prognosis and quality of life of patients, potentially leading to the interruption of cancer chemotherapy and compromising cancer treatment. Recently, onco-cardiology (or cardio-oncology) has developed as a new interdisciplinary field that focuses on the prevention and treatment of cardiovascular toxicity of anticancer drugs. In this review, we explore the mechanism underlying the cardiotoxicity of anthracyclines and examine pharmacological agents that safeguard the heart from anthracycline-induced damage. Anthracycline-induced cardiotoxicity primarily involves oxidative stress, characterized by radical production in mitochondria and subsequent apoptosis in cardiomyocytes. While various antioxidant agents, such as resveratrol, vitamin E, and melatonin have demonstrated efficacy in reducing anthracycline-induced cardiotoxicity in animal models, their clinical effectiveness remains inconclusive. Alternatively, dexrazoxane, an intracellular iron chelator, along with standard heart failure medications, such as β-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers, reduce anthracycline cardiotoxicity and prevent subsequent heart failure in both animal and human studies. Additionally, statins [hydroxymethylglutaryl (HMG)-CoA reductase inhibitors] and ranolazine have emerged as potential candidates for attenuating anthracycline-induced cardiotoxicity in clinical settings. Notably, recent in vitro findings suggest that everolimus, an autophagy/mitophagy-inducing antitumor drug, may protect cardiomyocytes from anthracycline-induced toxicity without reducing the antitumor effects of anthracycline. Although promising, further clinical research is warranted to validate the potential of everolimus as a safer and more effective anthracycline chemotherapeutic strategy.
许多抗癌药物,包括蒽环类药物,都存在作为不良反应导致心血管损伤的风险。这可能会对患者的预后和生活质量产生不利影响,有可能导致癌症化疗中断并危及癌症治疗。最近,肿瘤心脏病学(或心脏肿瘤学)作为一个新的跨学科领域发展起来,专注于预防和治疗抗癌药物的心血管毒性。在本综述中,我们探讨了蒽环类药物心脏毒性的潜在机制,并研究了保护心脏免受蒽环类药物诱导损伤的药物制剂。蒽环类药物诱导的心脏毒性主要涉及氧化应激,其特征是线粒体中产生自由基,随后心肌细胞发生凋亡。虽然各种抗氧化剂,如白藜芦醇、维生素E和褪黑素,已在动物模型中证明在降低蒽环类药物诱导的心脏毒性方面有效,但其临床效果仍无定论。相比之下,细胞内铁螯合剂右丙亚胺,与标准的心力衰竭药物,如β受体阻滞剂、血管紧张素转换酶抑制剂和血管紧张素II受体阻滞剂一起,在动物和人体研究中均能降低蒽环类药物的心脏毒性并预防随后的心力衰竭。此外,他汀类药物[羟甲基戊二酰辅酶A(HMG)-CoA还原酶抑制剂]和雷诺嗪已成为在临床环境中减轻蒽环类药物诱导的心脏毒性的潜在候选药物。值得注意的是,最近的体外研究结果表明,依维莫司,一种诱导自噬/线粒体自噬的抗肿瘤药物,可能保护心肌细胞免受蒽环类药物诱导的毒性,而不降低蒽环类药物的抗肿瘤作用。尽管前景广阔,但仍需要进一步的临床研究来验证依维莫司作为一种更安全、更有效的蒽环类化疗策略的潜力。