Adverse effects of tyrosine kinase inhibitors in cancer therapy: pathophysiology, mechanisms and clinical management

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Июль 7, 2023

Since their invention in the early 2000s, tyrosine kinase inhibitors (TKIs) have gained prominence as most effective pathway-directed anti-cancer agents. TKIs shown significant utility treatment of multiple hematological malignancies and solid tumors, including chronic myelogenous leukemia, non-small cell lung cancers, gastrointestinal stromal HER2-positive breast cancers. Given widespread applications, an increasing frequency TKI-induced adverse effects has been reported. Although are known to affect organs body lungs, liver, tract, kidneys, thyroid, blood, skin, cardiac involvement accounts for some serious complications. The frequently reported cardiovascular side range from hypertension, atrial fibrillation, reduced function, heart failure sudden death. potential mechanisms these unclear, leading critical knowledge gaps development therapy guidelines. There limited data infer best clinical approaches detection therapeutic modulation effects, universal consensus regarding various management guidelines is yet be reached. In this state-of-the-art review, we examine pre-clinical studies curate evidence on pathophysiology, mechanisms, reactions. We expect that review will provide researchers allied healthcare providers with up-to-date information natural history, risk stratification, emerging cancer patients.

Язык: Английский

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Therapeutic advances of targeting receptor tyrosine kinases in cancer

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Авг. 14, 2024

Abstract Receptor tyrosine kinases (RTKs), a category of transmembrane receptors, have gained significant clinical attention in oncology due to their central role cancer pathogenesis. Genetic alterations, including mutations, amplifications, and overexpression certain RTKs, are critical creating environments conducive tumor development. Following discovery, extensive research has revealed how RTK dysregulation contributes oncogenesis, with many subtypes showing dependency on aberrant signaling for proliferation, survival progression. These findings paved the way targeted therapies that aim inhibit crucial biological pathways cancer. As result, RTKs emerged as primary targets anticancer therapeutic Over past two decades, this led synthesis validation numerous small molecule kinase inhibitors (TKIs), now effectively utilized treating various types. In manuscript we provide comprehensive understanding context We explored alterations specific receptors across different malignancies, special dedicated examination current inhibitors, highlighting potential therapies. By integrating latest evidence, seek elucidate pivotal biology efficacy inhibition promising treatment outcomes.

Язык: Английский

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Hypertension and Prohypertensive Antineoplastic Therapies in Cancer Patients

Circulation Research, Год журнала: 2021, Номер 128(7), С. 1040 - 1061

Опубликована: Апрель 1, 2021

The development of a wide range novel antineoplastic therapies has improved the prognosis for patients with malignancies, which increased number cancer survivors substantially. Despite oncological benefit, are exposed to short- and long-term adverse cardiovascular toxicities associated anticancer therapies. Systemic hypertension, most common comorbidity among patients, is major contributor risk developing these events. Cancer hypertension have factors, overlapping pathophysiological mechanisms may also be factor some tumor types. Many prohypertensive effects. Although by agents lead been characterized, further preclinical clinical studies required investigate exact pathophysiology optimal management therapy. In this way, monitoring before, during, after treatment can minimize risks. This vital optimize health in survivors, ensure that advances terms survivorship do not come at expense toxicities.

Язык: Английский

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Mechanistic and Clinical Overview Cardiovascular Toxicity of BRAF and MEK Inhibitors

JACC CardioOncology, Год журнала: 2022, Номер 4(1), С. 1 - 18

Опубликована: Март 1, 2022

Rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors have revolutionized melanoma treatment. Approximately half of patients with harbor a BRAF gene mutation subsequent dysregulation the RAF-MEK-ERK signaling pathway. Targeting this pathway MEK blockade results in control cell proliferation and, most cases, disease control. These pathways also cardioprotective effects are necessary for normal vascular cardiac physiology. associated adverse cardiovascular including hypertension, left ventricular dysfunction, venous thromboembolism, atrial arrhythmia, electrocardiographic QT interval prolongation. may be underestimated clinical trials. Baseline assessment follow-up, serial imaging blood pressure assessment, essential to balance optimal anti-cancer therapy while minimizing side effects. In review, an overview BRAF/MEK inhibitor-induced toxicity, mechanisms underlying these, strategies surveillance, prevention, treatment these provided.

Язык: Английский

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Exploring the Spectrum of VEGF Inhibitors’ Toxicities from Systemic to Intra-Vitreal Usage in Medical Practice

Cancers, Год журнала: 2024, Номер 16(2), С. 350 - 350

Опубликована: Янв. 13, 2024

The use of Vascular Endothelial Growth Factor inhibitors (VEGFi) has become prevalent in the field medicine, given high incidence various pathological conditions necessitating VEGF inhibition within general population. These encompass a range advanced neoplasms, such as colorectal cancer, non-small cell lung renal ovarian and others, along with ocular diseases. utilization VEGFi is not without potential risks adverse effects, requiring healthcare providers to be well-prepared for identification management. can broadly categorized into two groups: antibodies or chimeric proteins that specifically target (bevacizumab, ramucirumab, aflibercept, ranibizumab, brolucizumab) non-selective selective small molecules (sunitinib, sorafenib, cabozantinib, lenvatinib, regorafenib, etc.) designed impede intracellular signaling receptor (RTKi, tyrosine kinase inhibitors). presentation mechanisms effects resulting from depend primarily on this distinction route drug administration (systemic intra-vitreal). This review provides thorough examination causes, recognition, management, preventive strategies toxicities goal offering support oncologists both clinical practice design trials.

Язык: Английский

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Mechanisms shared between cancer, heart failure, and targeted anti-cancer therapies

Cardiovascular Research, Год журнала: 2022, Номер 118(18), С. 3451 - 3466

Опубликована: Авг. 24, 2022

Heart failure (HF) and cancer are the leading causes of death worldwide accumulating evidence demonstrates that HF affect one another in a bidirectional way. Patients with at increased risk for developing cancer, is associated accelerated tumour growth. The presence malignancy may induce systemic metabolic, inflammatory, microbial alterations resulting impaired cardiac function. In addition to pathophysiologic mechanisms shared between HF, overlaps also exist pathways required normal physiology Therefore, these explain cardiotoxicity as result targeted anti-cancer therapies. This review provides an overview involved connection specifically focusing upon current 'hot-topics' mechanisms. It subsequently describes therapies cardiotoxic potential overlap their targets

Язык: Английский

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Cardiovascular Toxicities Associated with Tyrosine Kinase Inhibitors

Current Cardiology Reports, Год журнала: 2023, Номер 25(4), С. 269 - 280

Опубликована: Фев. 16, 2023

Язык: Английский

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Comparing cardiovascular adverse events in cancer patients: A meta-analysis of combination therapy with angiogenesis inhibitors and immune checkpoint inhibitors versus angiogenesis inhibitors alone

Critical Reviews in Oncology/Hematology, Год журнала: 2023, Номер 188, С. 104059 - 104059

Опубликована: Июнь 21, 2023

Язык: Английский

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Cardiotoxicity of BRAF/MEK Inhibitors

JACC CardioOncology, Год журнала: 2023, Номер 5(5), С. 628 - 637

Опубликована: Июнь 7, 2023

Rapidly accelerated fibrosarcoma B-type (BRAF) and mitogen-activated extracellular signal-regulated kinase (MEK) inhibitors have revolutionized treatment for patients with BRAF-mutated melanoma. Although left ventricular systolic dysfunction associated these therapies has been reported in clinical trials, the real-world incidence is poorly defined, as are risk factors its development.This study sought to characterize incidence, time course, cancer therapy-related cardiac (CTRCD) melanoma receiving BRAF MEK inhibitors.Patients treated at a hospital network between June 1, 2017, 30, 2020, were included retrospectively. CTRCD was defined mild, moderate, or severe according International Cardio-Oncology Society (ICOS) definitions. Baseline cardiotoxicity stratification performed using Heart Failure Association/ICOS tool.Of 63 included, 27% developed (17% mild 10% moderate). No symptomatic heart failure. occurred most frequently considered be "low" "medium" baseline of (82%). The ejection fraction global longitudinal strain not different who moderate vs those did not. Left internal diameters diastole systole larger compared (left diameter diastole: 4.9 ± 0.6 cm 4.3 cm; P = 0.023; systole: 3.3 0.4 2.8 0.5 0.039).BRAF inhibitor-associated common. utility tool appears limited this group, better prediction tools needed. long-term consequences CTRCD, particularly warrant evaluation prospective studies.

Язык: Английский

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Established and Emerging Cancer Therapies and Cardiovascular System: Focus on Hypertension—Mechanisms and Mitigation

Hypertension, Год журнала: 2023, Номер 80(4), С. 685 - 710

Опубликована: Фев. 9, 2023

Cardiovascular disease and cancer are 2 of the leading causes death worldwide. Although improvements in outcomes have been noted for both entities, success therapies has come at cost times very impactful adverse events such as cardiovascular events. Hypertension both, a side effect well risk factor cardiotoxicity therapies. Some these dynamics keeping with role hypertension not only heart failure, but also development coronary cerebrovascular disease, kidney its association higher morbidity mortality overall. Other aspects molecular mechanisms underlying amplification acute long-term anthracyclines increase blood pressure various therapeutics remain to be elucidated. In this review, we cover latest clinical data regarding across spectrum novel anticancer known or postulated pathophysiological mechanisms. Furthermore, review implications drugs commonly associated anthracyclines. An outline management strategies, including pharmacological lifestyle interventions models care aimed facilitate early detection more timely patients survivors concludes which overall aims improve cancer-specific outcomes.

Язык: Английский

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