Division of Cardiology, Johns Hopkins School of Medicine, Baltimore, MD (V.S.H.).
Cardio-Oncology Center of Excellence, Washington University, St Louis, MO (K.W.Z., D.J.L.).
Circ Res. 2021 May 14;128(10):1576-1593. doi: 10.1161/CIRCRESAHA.121.318223. Epub 2021 May 13.
Oncology has seen growing use of newly developed targeted therapies. Although this has resulted in dramatic improvements in progression-free and overall survival, challenges in the management of toxicities related to longer-term treatment of these therapies have also become evident. Although a targeted approach often exploits the differences between cancer cells and noncancer cells, overlap in signaling pathways necessary for the maintenance of function and survival in multiple cell types has resulted in systemic toxicities. In particular, cardiovascular toxicities are of important concern. In this review, we highlight several targeted therapies commonly used across a variety of cancer types, including HER2 (human epidermal growth factor receptor 2)+ targeted therapies, tyrosine kinase inhibitors, immune checkpoint inhibitors, proteasome inhibitors, androgen deprivation therapies, and MEK (mitogen-activated protein kinase kinase)/BRAF (v-raf murine sarcoma viral oncogene homolog B) inhibitors. We present the oncological indications, heart failure incidence, hypothesized mechanisms of cardiotoxicity, and potential mechanistic rationale for specific cardioprotective strategies.
肿瘤学领域越来越多地使用新开发的靶向治疗方法。尽管这导致无进展生存期和总生存期的显著改善,但与这些治疗方法的长期治疗相关的毒性管理方面的挑战也变得明显。尽管靶向方法通常利用癌细胞和非癌细胞之间的差异,但为维持多种细胞类型的功能和存活所需的信号通路重叠导致了全身毒性。特别是,心血管毒性是一个重要的关注点。在这篇综述中,我们强调了几种常见的靶向治疗方法,这些方法用于多种癌症类型,包括 HER2(人表皮生长因子受体 2)靶向治疗、酪氨酸激酶抑制剂、免疫检查点抑制剂、蛋白酶体抑制剂、雄激素剥夺疗法和 MEK(丝裂原激活蛋白激酶激酶)/BRAF(v-raf 鼠肉瘤病毒癌基因同源物 B)抑制剂。我们介绍了肿瘤学适应证、心力衰竭发生率、推测的心脏毒性机制以及特定心脏保护策略的潜在机制合理性。