Gopal Srila, Miller Kenneth B, Jaffe Iris Z
Department of Medicine, Division of Hematology/Oncology, Tufts Medical Center, Boston, MA 02111, U.S.A. Molecular Cardiology Research Institute, Tufts Medical Center, Boston, MA 02111, U.S.A.
Department of Medicine, Division of Hematology/Oncology, Tufts Medical Center, Boston, MA 02111, U.S.A.
Clin Sci (Lond). 2016 Oct 1;130(20):1763-79. doi: 10.1042/CS20160246.
Molecularly targeted anti-cancer therapies have revolutionized cancer treatment by improving both quality of life and survival in cancer patients. However, many of these drugs are associated with cardiovascular toxicities that are sometimes dose-limiting. Moreover, the long-term cardiovascular consequences of these drugs, some of which are used chronically, are not yet known. Although the scope and mechanisms of the cardiac toxicities are better defined, the mechanisms for vascular toxicities are only beginning to be elucidated. This review summarizes what is known about the vascular adverse events associated with three classes of novel anti-cancer therapies: vascular endothelial growth factor (VEGF) inhibitors, breakpoint cluster-Abelson (BCR-ABL) kinase inhibitors used to treat chronic myelogenous leukaemia (CML) and immunomodulatory agents (IMiDs) used in myeloma therapeutics. Three of the best described vascular toxicities are reviewed including hypertension, increased risk of acute cardiovascular ischaemic events and arteriovenous thrombosis. The available data regarding the mechanism by which each therapy causes vascular complication are summarized. When data are limited, potential mechanisms are inferred from the known effects of inhibiting each target on vascular cell function and disease. Enhanced understanding of the molecular mechanisms of vascular side effects of targeted cancer therapy is necessary to effectively manage cancer patients and to design safer targeted cancer therapies for the future.
分子靶向抗癌疗法通过改善癌症患者的生活质量和生存率，彻底改变了癌症治疗方式。然而，这些药物中的许多都与心血管毒性有关，有时这些毒性会限制剂量。此外，这些药物（其中一些是长期使用的）的长期心血管后果尚不清楚。尽管心脏毒性的范围和机制已得到更好的界定，但血管毒性的机制才刚刚开始被阐明。本综述总结了关于与三类新型抗癌疗法相关的血管不良事件的已知情况：血管内皮生长因子（VEGF）抑制剂、用于治疗慢性粒细胞白血病（CML）的断裂簇集区-阿贝尔森（BCR-ABL）激酶抑制剂以及用于骨髓瘤治疗的免疫调节剂（IMiDs）。本文综述了三种描述最为详尽的血管毒性，包括高血压、急性心血管缺血事件风险增加以及动静脉血栓形成。总结了关于每种疗法导致血管并发症的机制的现有数据。当数据有限时，从抑制每个靶点对血管细胞功能和疾病的已知影响中推断潜在机制。深入了解靶向癌症治疗血管副作用的分子机制对于有效管理癌症患者和设计未来更安全的靶向癌症疗法是必要的。
