快速加速的纤维肉瘤B型(BRAF)和丝裂原激活的细胞外信号调节激酶(MEK)抑制剂彻底改变了黑色素瘤的治疗。大约一半的黑色素瘤患者存在BRAF基因突变,随后RAF-MEK-ERK信号通路失调。用BRAF和MEK阻断靶向此途径可控制细胞增殖,在大多数情况下,疾病控制。这些途径还具有心脏保护作用,并且是正常血管和心脏生理学所必需的。BRAF和MEK抑制剂与包括高血压在内的不良心血管作用有关,左心功能不全,静脉血栓栓塞,房性心律失常,心电图QT间期延长。这些影响在临床试验中可能被低估了。基线心血管评估和随访,包括连续成像和血压评估,对于平衡最佳抗癌治疗,同时最大限度地减少心血管副作用至关重要。在这次审查中,概述BRAF/MEK抑制剂诱导的心血管毒性,这些背后的机制,和监视策略,预防,并提供这些影响的治疗。
Rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors have revolutionized melanoma treatment. Approximately half of patients with melanoma harbor a BRAF gene mutation with subsequent dysregulation of the RAF-MEK-ERK signaling pathway. Targeting this pathway with BRAF and MEK blockade results in control of cell proliferation and, in most cases, disease control. These pathways also have cardioprotective effects and are necessary for normal vascular and cardiac physiology. BRAF and MEK inhibitors are associated with adverse cardiovascular effects including hypertension, left ventricular dysfunction, venous thromboembolism, atrial arrhythmia, and electrocardiographic QT interval prolongation. These effects may be underestimated in clinical trials. Baseline cardiovascular assessment and follow-up, including serial imaging and blood pressure assessment, are essential to balance optimal anti-cancer therapy while minimizing cardiovascular side effects. In this
review, an overview of BRAF/MEK inhibitor-induced cardiovascular toxicity, the mechanisms underlying these, and strategies for surveillance, prevention, and treatment of these effects are provided.