Cardiovascular toxicities of BCR-ABL tyrosine kinase inhibitors in chronic myeloid leukemia: preventive strategies and cardiovascular surveillance

Aghel, Nazanin; Delgado, Diego; Lipton, Jeffrey H.

doi:10.2147/vhrm.s108874

Cited by 68 publications

(86 citation statements)

References 85 publications

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“…Nilotinib is an orally bioavailable drug used in CML patients resistant to previous therapies. Although during the very first clinical study, no relevant vascular adverse effects were observed, several other clinical studies over the last 5 years have demonstrated an increased risk of peripheral artery disease (PAD) [52]. This adverse event has been related to the metabolic effect of nilotinib and to its influence on the endothelium, platelets, and on the coagulation process [14,52].…”

Section: Anti-bcr-abl Agentsmentioning

confidence: 99%

MicroRNAs in Cancer Treatment-Induced Cardiotoxicity

Pellegrini

Sileno

D'agostino

et al. 2020

Cancers

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Cancer treatment has made significant progress in the cure of different types of tumors. Nevertheless, its clinical use is limited by unwanted cardiotoxicity. Aside from the conventional chemotherapy approaches, even the most newly developed, i.e., molecularly targeted therapy and immunotherapy, exhibit a similar frequency and severity of toxicities that range from subclinical ventricular dysfunction to severe cardiomyopathy and, ultimately, congestive heart failure. Specific mechanisms leading to cardiotoxicity still remain to be elucidated. For instance, oxidative stress and DNA damage are considered key players in mediating cardiotoxicity in different treatments. microRNAs (miRNAs) act as key regulators in cell proliferation, cell death, apoptosis, and cell differentiation. Their dysregulation has been associated with adverse cardiac remodeling and toxicity. This review provides an overview of the cardiotoxicity induced by different oncologic treatments and potential miRNAs involved in this effect that could be used as possible therapeutic targets.Cancers 2020, 12, 704 2 of 24 circulating miRNAs have been used as excellent biomarkers in different studies and can be used as biomarkers for cardiovascular diseases (CVDs) [5]. Moreover, miRNA deregulation is often associated with tumor progression, and many anticancer treatments affect miRNA expression. In this review we aimed to discuss relevant miRNAs modulated by therapies for cancer that have been demonstrated to be involved in CVD. In the following paragraphs, we provide an overview of the most important anticancer treatments that are known to induce cardiotoxicity. Anticancer Treatment and CardiotoxicityAnticancer treatment has accomplished remarkable progress in the last century resulting in improved quality of life and survival rates of cancer patients. These advances in cancer treatment, however, have been often accompanied by therapy-related complications, including secondary side effects on the whole organism [6].The most commonly used cancer therapeutics in modern medicine include the traditional surgery, radiotherapy, and conventional chemotherapy approaches; moreover, two new therapeutic modalities have been introduced in recent decades, namely molecularly targeted therapy and immunotherapy [7], as summarized in Figure 1. Traditional chemotherapy agents consist of non-specific cytotoxic treatments (e.g., alkylating agents and antimetabolites) that rapidly eliminate replicating cells, including not only tumor cells but also normal tissue cells, with a broad range of side effects that significantly limit their applications in cancer therapy. In contrast to conventional systemic chemotherapy, molecularly targeted cancer therapies, using novel drugs aimed at the inhibition of intracellular signaling pathways fundamental for cancer proliferation or differentiation (e.g., monoclonal antibodies and low molecular weight protein-kinase inhibitors), are thought to be cancer-specific, with fewer associated adverse effects on normal cells [8]. Lastly, immunother...

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Section: Anti-bcr-abl Agentsmentioning

confidence: 99%

MicroRNAs in Cancer Treatment-Induced Cardiotoxicity

Pellegrini

Sileno

D'agostino

et al. 2020

Cancers

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“…For correspondence: Prof. Gennadii Efimovich Gendlin, MD, PhD, 1 Ostrovityanova str., Moscow, Russian Federation, 117997; e-mail: rgmugt2@mail.ru КЛИНИЧЕСКАЯ ОНКОГЕМАТОЛОГИЯ при его применении выявлялось крайне редко (< 1 % случаев), и она была связана с наличием в анамнезе у некоторых больных ХМЛ сердечно-сосудистой патологии [3]. Более того, в отдельных исследованиях отмечается положительное метаболическое и сосудистое действие иматиниба [4].…”

Section: Received: September 8 2019unclassified

Comparative Analysis of Cardiovascular Disorders in Patients with Chronic Myeloid Leukemia on Tyrosine Kinase Inhibitor Therapy

Макеева¹,

Емелина²,

Bykova³

et al. 2020

Клиническая онкогематология

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Цель. Анализ нежелательных сердечно-сосудистых явлений у больных хроническим миелолейкозом (ХМЛ), получавших различные ингибиторы тирозинкиназы (ИТК). Материалы и методы. В исследование включено 97 пациентов с ХМЛ, имевших показания к назначению нилотиниба, дазатиниба или иматиниба. Ко времени обследования пациенты получали лечение ИТК в течение 1-138 мес. Из них 3 больных на протяжении наблюдения получали последовательно 2 препарата. Все пациенты с ХМЛ были в возрасте 22-79 лет (медиана 53,5 года): 55 женщин в возрасте 22-71 год (медиана 53,5 года) и 42 мужчины в возрасте 24-79 лет (медиана 53 года). Результаты. Сравнительный анализ показал статистически значимо большее влияние нилотиниба на продолжительность максимального суточного интервала QTc по сравнению с другими ИТК. У пациентов, получавших нилотиниб (n = 15), при сроке приема более 38 мес. QTc был 0,47 с (межквартильный интервал [МКИ] 0,46-0,47 с), в группе иматиниба (n = 17)-0,43 с (МКИ 0,43-0,44 с), дазатиниба (n = 4)-0,43 с (МКИ 0,42-0,44 с) (p = 0,0008). Доля больных с QTc > 0,46 с среди всех получавших нилотиниб составила 62 % (31/50), в группах иматиниба (6/41) и дазатиниба (2/18)-14,6 и 11,1 % соответственно (p = 0,0008). У 5 пациентов QTc был более 0,48 с, что служит показанием к прекращению лечения или к редукции дозы препарата. У 2 пациентов выявленные изменения продолжительности интервала QTc потребовали временной отмены ИТК. При отмене или снижении дозы нилотиниба во всех

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“…К наиболее изученным киназам, в отношении которых активны ИТК, применяемые при ХМЛ, относятся BRAF, FMS, EGFR, PDGFR, PYK2, TIE2, VEGFR1/2/3 [44]. Многие киназы участвуют в регуляции деятельности эндотелия сосудов, а также функции сердечно-сосудистой системы и миокарда [7].…”

Section: механизмы кардиоваскулярной токсичности иткunclassified

“…В связи с этим риск возникновения сердечно-сосудистых НЯ у них был изначально высоким [63]. Учитывая, что атеросклеротическое поражение сосудов распространено среди населения в целом и у пациентов с ХМЛ [67], изучение патофизиологических механизмов развития ССЗ представляется особенно актуальным [7].…”

Section: патофизиология развития сердечно-сосудистых заболеваний: патunclassified

“…Механизмы развития кардиоваскулярной токсичности при терапии ИТК предположительно связаны с внецелевым (офф-таргетным) действием этих препаратов на другие белки-киназы и продолжают изучаться [6][7][8]. В качестве возможных механизмов обсуждается воздействие на эндотелий сосудистой стенки, функциональное состояние тромбоцитов, а также метаболизм липидов и глюкозы, что в совокупности может приводить к раннему возникновению атеросклероза как одного из основных факторов развития сердечно-сосудистых заболеваний (ССЗ).…”

Section: Introductionunclassified

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Cardiovascular Toxicity of Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia

Давыдкин

Наумова

Осадчук

et al. 2018

Клиническая онкогематология

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In the present review the cardiovascular complications in patients with chronic myeloid leukemia (CML) receiving tyrosine kinase inhibitors (TKI) are discussed. It covers current views on pathogenesis of TKI cardiovascular toxicity. The pathophysiology of cardiovascular diseases (CVD) is considered as a part of the so-called pathophysiological continuum, i.e. a complex of processes developing at the molecular and cellular levels before clinical symptoms of the above diseases occur. Cardiovascular toxicity of certain TKIs can contribute to progression of pathophysiological processes in CML patients. The study of mechanisms underlying cardiovascular complications of TKI-based therapy is essential for evaluating the risks of their development in each patient. Identification of CVD predictors during TKI-based therapy can allow to elaborate a scheme for cardiovascular monitoring and safe patient management under consideration of individual risks and to avoid severe life-threatening complications.

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Cardiovascular toxicities of BCR-ABL tyrosine kinase inhibitors in chronic myeloid leukemia: preventive strategies and cardiovascular surveillance

Cited by 68 publications

References 85 publications

MicroRNAs in Cancer Treatment-Induced Cardiotoxicity

MicroRNAs in Cancer Treatment-Induced Cardiotoxicity

Comparative Analysis of Cardiovascular Disorders in Patients with Chronic Myeloid Leukemia on Tyrosine Kinase Inhibitor Therapy

Cardiovascular Toxicity of Tyrosine Kinase Inhibitors in Patients with Chronic Myeloid Leukemia

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