Brown S-A, Nhola L, Herrmann J
Department of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota, USA.
Clin Pharmacol Ther. 2017 Jan;101(1):65-80. doi: 10.1002/cpt.552. Epub 2016 Nov 26.
Once universally considered a rapidly fatal condition, cancer has increasingly become a chronic medical condition and comorbidities and adverse effects of cancer therapies have become increasingly significant. One of the leading advancements that has gained traction for the treatment of a variety of malignancies is the class of small molecule tyrosine kinase inhibitors (TKIs). Although, in many aspects revolutionary, TKIs have their own profile of side effects, including cardiovascular side effects, the most common being hypertension (HTN), congestive heart failure, corrected QT (QTc) prolongation, and instances of premature coronary heart disease. Herein, we describe the mechanisms of small TKI-induced cardiovascular toxicity and related intracellular signaling. In particular, systems-based approaches to the understanding of small TKI-induced cardiovascular toxicity are addressed. The pathophysiology of synergic cardiovascular toxicity from TKIs, anthracyclines, and monoclonal antibodies (e.g., trastuzumab, bevacizumab) is illustrated. Finally, recommendations are made for implementing systems medicine in clinical practice, for individualized cardiovascular wellness after cancer therapy.
癌症曾一度被普遍认为是一种迅速致命的疾病，如今它越来越多地成为一种慢性疾病，癌症治疗的合并症和副作用也变得越来越显著。小分子酪氨酸激酶抑制剂（TKIs）是治疗多种恶性肿瘤方面得到广泛应用的主要进展之一。尽管TKIs在许多方面具有革命性，但它们也有自己的副作用，包括心血管副作用，最常见的是高血压（HTN）、充血性心力衰竭、校正QT（QTc）延长以及早发性冠心病病例。在此，我们描述小分子TKI诱导的心血管毒性机制及相关的细胞内信号传导。特别讨论了基于系统的方法来理解小分子TKI诱导的心血管毒性。阐述了TKIs、蒽环类药物和单克隆抗体（如曲妥珠单抗、贝伐单抗）协同心血管毒性的病理生理学。最后，针对在临床实践中实施系统医学以及癌症治疗后个体化心血管健康提出了建议。
