Cardiovascular toxic effects of targeted cancer therapy

Abstract

Over the past decade, there has been a major shift in chemotherapy from non-specific cytotoxic drugs to molecular targeted drug therapies. As more molecular targeted therapies are developed, new types of cardiovascular toxicities induced by targeted therapies are a growing problem. Cardiotoxicity induced by the human epidermal growth factor receptor-2 inhibitor trastuzumab manifests as decreased left ventricular ejection fraction. In contrast to anthracycline treatment, most cardiac events occur during trastuzumab treatment, but are reversed quickly when treatment is interrupted and cardiac intervention is established.

Vasospastic angina in a chronic myeloid leukemia patient treated with nilotinib

“…Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by a genetic translocation between chromosomes 9 and 22, leading to the generation of the hybrid protein BCR-ABL with tyrosine kinase activity. For most CML patients, the introduction of BCR-ABL tyrosine kinase inhibitors (TKIs) has changed this fatal disease into a manageable chronic condition [ 1 , 2 ]. However, recent studies have revealed that patients treated with newer BCR-ABL TKIs show a significant increase in the incidence of vascular adverse events, including increased blood pressure, venous thrombosis, progressive atherosclerosis with coronary artery disease, and peripheral arterial obstructive disease [ 2 , 3 ].…”

“…For most CML patients, the introduction of BCR-ABL tyrosine kinase inhibitors (TKIs) has changed this fatal disease into a manageable chronic condition [ 1 , 2 ]. However, recent studies have revealed that patients treated with newer BCR-ABL TKIs show a significant increase in the incidence of vascular adverse events, including increased blood pressure, venous thrombosis, progressive atherosclerosis with coronary artery disease, and peripheral arterial obstructive disease [ 2 , 3 ]. Nilotinib, a second-generation TKI, is highly effective in the treatment of CML patients both as a first-line treatment and after imatinib treatment failure; however, it is known to be more vasculotoxic than older TKIs, including imatinib [ 2 ].…”

“…However, recent studies have revealed that patients treated with newer BCR-ABL TKIs show a significant increase in the incidence of vascular adverse events, including increased blood pressure, venous thrombosis, progressive atherosclerosis with coronary artery disease, and peripheral arterial obstructive disease [ 2 , 3 ]. Nilotinib, a second-generation TKI, is highly effective in the treatment of CML patients both as a first-line treatment and after imatinib treatment failure; however, it is known to be more vasculotoxic than older TKIs, including imatinib [ 2 ]. Herein, we present a rare case of nilotinib-associated vasospastic angina confirmed by an acetylcholine (ACh) spasm provocation test.…”

RIP1/RIP3/MLKL-mediated necroptosis contributes to vinblastine-induced myocardial damage

“…Traditional chemotherapeutic drugs, such as platinum, doxorubicin, have historically been a major problem that causes cardiotoxicity. Molecular targeted therapy agents, including tyrosine kinase inhibitors (TKIs) lapatinib, sorafenib, imatinib and humanized monoclonal antibodies trastuzumab, bevacizumab, are known to cause cardiovascular toxic effects [3,4]. The recent immunotherapeutic agents such as checkpoint inhibitors (e.g., ipilimumab, nivolumab and atezolizumab), though exhibiting a highly promising therapeutic effect with durable anti-cancer responses and long-term remission in a broad spectrum of cancers, have also been found to cause cardiac dysfunction [5].…”

“…The recent immunotherapeutic agents such as checkpoint inhibitors (e.g., ipilimumab, nivolumab and atezolizumab), though exhibiting a highly promising therapeutic effect with durable anti-cancer responses and long-term remission in a broad spectrum of cancers, have also been found to cause cardiac dysfunction [5]. The common cardiac toxic effects caused by anti-cancer therapies include left ventricular dysfunction (LVD), heart failure (HF), stoke, myocardial ischemia, myocarditis, cardiomyopathy [3][4][5] and so on. For example, platinum-based compounds can induce cardiac endothelial dysfunction, leading to myocardial ischemia and stoke [6].…”