UCSF Department of Medicine, Division of Cardiology, Section of Cardio-Oncology and Immunology, United States of America.
J Mol Cell Cardiol. 2022 Apr;165:64-75. doi: 10.1016/j.yjmcc.2021.12.013. Epub 2022 Jan 1.
Cardio-oncology is a rapidly growing field in cardiology that focuses on the management of cardiovascular toxicities associated with cancer-directed therapies. Tumor hypoxia is a central driver of pathologic tumor growth, metastasis, and chemo-resistance. In addition, conditions that mimic hypoxia (pseudo-hypoxia) play a causal role in the pathogenesis of numerous types of cancer, including renal cell carcinoma. Therefore, therapies targeted at hypoxia signaling pathways have emerged over the past several years. Though efficacious, these therapies are associated with significant cardiovascular toxicities, ranging from hypertension to cardiomyopathy. This review focuses on oxygen metabolism in tumorigenesis, the role of targeting hypoxia signaling in cancer therapy, and the relevance of oxygen metabolism in cardio-oncology. This review will specifically focus on hypoxia signaling mediated by hypoxia-inducible factors and the prolyl hydroxylase oxygen-sensing enzymes, the cardiovascular effects of specific cancer targeted therapies mediated on VEGF and HIF signaling, hypoxic signaling in cardiovascular disease, and the role of oxygen in anthracycline cardiotoxicity. The implications of these therapies on myocardial biology and cardiac function are discussed, underlining the fine balance of hypoxia signaling in cardiac homeostasis. Understanding these cardiovascular toxicities will be important to optimize treatment for cancer patients while mitigating potentially severe cardiovascular side effects.
肿瘤心脏病学是心脏病学中一个快速发展的领域，专注于管理癌症靶向治疗相关的心血管毒性。肿瘤缺氧是病理性肿瘤生长、转移和化疗耐药的主要驱动因素。此外，模拟缺氧的条件（假性缺氧）在多种类型的癌症发病机制中起着因果作用，包括肾细胞癌。因此，过去几年出现了针对缺氧信号通路的治疗方法。虽然这些治疗方法有效，但它们与严重的心血管毒性相关，范围从高血压到心肌病。这篇综述重点介绍肿瘤发生中的氧代谢、靶向缺氧信号在癌症治疗中的作用以及氧代谢在肿瘤心脏病学中的相关性。这篇综述将特别关注缺氧诱导因子介导的缺氧信号和脯氨酰羟化酶氧感应酶、血管内皮生长因子和缺氧诱导因子信号介导的特定癌症靶向治疗的心血管效应、心血管疾病中的缺氧信号以及氧在蒽环类药物心脏毒性中的作用。讨论了这些治疗方法对心肌生物学和心脏功能的影响，强调了缺氧信号在心脏稳态中的精细平衡。了解这些心血管毒性对于优化癌症患者的治疗同时减轻潜在严重的心血管副作用非常重要。
