Department of Experimental and Clinical Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, D-20246 Hamburg, Germany.
Eur J Heart Fail. 2011 Jan;13(1):1-10. doi: 10.1093/eurjhf/hfq213.
The reductions in mortality and morbidity being achieved among cancer patients with current therapies represent a major achievement. However, given their mechanisms of action, many anti-cancer agents may have significant potential for cardiovascular side effects, including the induction of heart failure. The magnitude of this problem remains unclear and is not readily apparent from current clinical trials of emerging targeted agents, which generally under-represent older patients and those with significant co-morbidities. The risk of adverse events may also increase when novel agents, which frequently modulate survival pathways, are used in combination with each other or with other conventional cytotoxic chemotherapeutics. The extent to which survival and growth pathways in the tumour cell (which we seek to inhibit) coincide with those in cardiovascular cells (which we seek to preserve) is an open question but one that will become ever more important with the development of new cancer therapies that target intracellular signalling pathways. It remains unclear whether potential cardiovascular problems can be predicted from analyses of such basic signalling mechanisms and what pre-clinical evaluation should be undertaken. The screening of patients, optimization of therapeutic schemes, monitoring of cardiovascular function during treatment, and the management of cardiovascular side effects are likely to become increasingly important in cancer patients. This paper summarizes the deliberations of a cross-disciplinary workshop organized by the Heart Failure Association of the European Society of Cardiology (held in Brussels in May 2009), which brought together clinicians working in cardiology and oncology and those involved in basic, translational, and pharmaceutical science.
目前的癌症疗法在降低死亡率和发病率方面取得了重大成就。然而，鉴于它们的作用机制，许多抗癌药物可能具有显著的心血管副作用潜力，包括心力衰竭的诱导。这个问题的严重程度尚不清楚，也不容易从新兴靶向药物的当前临床试验中看出，这些临床试验通常代表性不足，代表性不足的是老年患者和有严重合并症的患者。当经常调节存活途径的新型药物与其他药物联合使用时，或者与其他常规细胞毒性化学疗法联合使用时，不良事件的风险也可能增加。肿瘤细胞中的存活和生长途径（我们试图抑制）与心血管细胞中的存活和生长途径（我们试图保护）之间的吻合程度是一个悬而未决的问题，但随着针对细胞内信号通路的新癌症疗法的发展，这个问题将变得越来越重要。尚不清楚是否可以从对这些基本信号机制的分析中预测潜在的心血管问题，以及应该进行哪些临床前评估。对患者进行筛选、优化治疗方案、在治疗过程中监测心血管功能以及处理心血管副作用，可能在癌症患者中变得越来越重要。本文总结了由欧洲心脏病学会心力衰竭协会（ESC）组织的一次跨学科研讨会的讨论结果（2009 年 5 月在布鲁塞尔举行），该研讨会汇集了从事心脏病学和肿瘤学工作的临床医生，以及从事基础、转化和药物科学的研究人员。
