Department of Medicine, University of Texas Health Science Center at Tyler-CHRISTUS Good Shepherd Medical Center, Longview, TX 75601, USA.
Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN 55905, USA.
Int J Mol Sci. 2020 Jan 17;21(2):604. doi: 10.3390/ijms21020604.
As many novel cancer therapies continue to emerge, the field of Cardio-Oncology (or onco-cardiology) has become crucial to prevent, monitor and treat cancer therapy-related cardiovascular toxicity. Furthermore, given the narrow therapeutic window of most cancer therapies, drug-drug interactions are prevalent in the cancer population. Consequently, there is an increased risk of affecting drug efficacy or predisposing individual patients to adverse side effects. Here we review the role of cytochrome P450 (CYP450) enzymes in the field of Cardio-Oncology. We highlight the importance of cardiac medications in preventive Cardio-Oncology for high-risk patients or in the management of cardiotoxicities during or following cancer treatment. Common interactions between Oncology and Cardiology drugs are catalogued, emphasizing the impact of differential metabolism of each substrate drug on unpredictable drug bioavailability and consequent inter-individual variability in treatment response or development of cardiovascular toxicity. This inter-individual variability in bioavailability and subsequent response can be further enhanced by genomic variants in CYP450, or by modifications of CYP450 gene, RNA or protein expression or function in various 'omics' related to precision medicine. Thus, we advocate for an individualized approach to each patient by a multidisciplinary team with clinical pharmacists evaluating a treatment plan tailored to a practice of precision Cardio-Oncology. This review may increase awareness of these key concepts in the rapidly evolving field of Cardio-Oncology.
随着越来越多的新型癌症疗法不断涌现，心血管肿瘤学（或肿瘤心脏病学）领域对于预防、监测和治疗癌症治疗相关的心血管毒性变得至关重要。此外，鉴于大多数癌症疗法的治疗窗口狭窄，癌症患者中药物相互作用很常见。因此，这会增加影响药物疗效或使个体患者易发生不良反应的风险。在这里，我们回顾了细胞色素 P450（CYP450）酶在心血管肿瘤学领域中的作用。我们强调了心脏药物在高风险患者的预防性心血管肿瘤学中的重要性，或在癌症治疗期间或之后管理心脏毒性方面的重要性。我们对肿瘤学和心脏病学药物之间的常见相互作用进行了分类，强调了每种底物药物的代谢差异对不可预测的药物生物利用度以及随后的个体间治疗反应或心血管毒性发展的影响。这种生物利用度和随后反应的个体间可变性可以通过 CYP450 的基因组变异，或通过 CYP450 基因、RNA 或蛋白质表达或功能的各种与精准医学相关的“组学”修饰进一步增强。因此，我们提倡由多学科团队对每个患者进行个体化治疗，其中临床药师评估针对精准心血管肿瘤学实践定制的治疗计划。这篇综述可能会提高人们对心血管肿瘤学这一快速发展领域中这些关键概念的认识。
