Cardiovascular Toxicities of Antiangiogenic Tyrosine Kinase Inhibitors: A Retrospective, Pharmacovigilance Study

Goldman, Adam; Bomze, David; Dankner, Rachel; Fourey, Dana; Boursi, Ben; Arad, Michael; Maor, Elad

doi:10.1007/s11523-021-00817-2

Cited by 21 publications

(23 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are two basic pharmacological mechanisms of the VSP inhibitors: monoclonal antibodies against the extracellular VSP components and inhibition of the intracellular domain of the tyrosine kinase (VEGFRs). The second mechanism is not specific because tyrosine kinases are used by many signalling systems [66]. Not surprisingly, such drugs have significant cardiovascular toxicities, which are not surprising due to the crucial role of VEGF in the development and functions of the vasculature and heart.…”

Section: Vegf As a Therapeutic Targetmentioning

confidence: 99%

The Role of the VEGF Family in Atherosclerosis Development and Its Potential as Treatment Targets

Dabravolski

Khotina

Omelchenko

et al. 2022

IJMS

View full text Add to dashboard Cite

The vascular endothelial growth factor (VEGF) family, the crucial regulator of angiogenesis, lymphangiogenesis, lipid metabolism and inflammation, is involved in the development of atherosclerosis and further CVDs (cardiovascular diseases). This review discusses the general regulation and functions of VEGFs, their role in lipid metabolism and atherosclerosis development and progression. These functions present the great potential of applying the VEGF family as a target in the treatment of atherosclerosis and related CVDs. In addition, we discuss several modern anti-atherosclerosis VEGFs-targeted experimental procedures, drugs and natural compounds, which could significantly improve the efficiency of atherosclerosis and related CVDs’ treatment.

show abstract

Section: Vegf As a Therapeutic Targetmentioning

confidence: 99%

The Role of the VEGF Family in Atherosclerosis Development and Its Potential as Treatment Targets

Dabravolski

Khotina

Omelchenko

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Lenvatinib is a small molecule tyrosine kinase inhibitor and clinically used for the treatment of radio‐iodide refractory differentiated thyroid cancer and other cancers. Related clinical reports suggested that lenvatinib had a serious risk of hypertension and cardiotoxicity, with mitochondrial toxicity in H9c2 cardiomyoblastic cell line exposed to lenvatinib 18–21 . With the increasing clinical use of lenvatinib, the effects of the parent and its metabolites discharged into the water on non‐target organisms should be taken into account.…”

Section: Discussionmentioning

confidence: 99%

“…Related clinical reports suggested that lenvatinib had a serious risk of hypertension and cardiotoxicity, with mitochondrial toxicity in H9c2 cardiomyoblastic cell line exposed to lenvatinib. [18][19][20][21] With the increasing clinical use of lenvatinib, the effects of the parent and its metabolites discharged into the water on non-target organisms should be taken into account. Here, we used zebrafish embryos to evaluate its cardiovascular effects.…”

Section: Discussionmentioning

confidence: 99%

Lenvatinib induces cardiac developmental toxicity in zebrafish embryos through regulation of Notch mediated‐oxidative stress generation

Liu

Huang

Wan

et al. 2022

Environmental Toxicology

View full text Add to dashboard Cite

Due to an increasing number of abused drugs dumped into the wastewater, more and more drugs are detected in the water environment, which may affect the survival of aquatic organisms. Lenvatinib is a multi-targeted tyrosine kinase inhibitor, and is clinically used to treat differentiated thyroid cancer, renal epithelial cell carcinoma and liver cancer. However, there are few reports on the effects of lenvatinib in embryos development. In this study, zebrafish embryos were used to evaluate the effect of lenvatinib on cardiovascular development. Well-developed zebrafish embryos were selected at 6 h post fertilization (hpf) and exposed to 0.05 mg/L, 0.1 mg/L and 0.2 mg/L lenvatinib up to 72 hpf. The processed embryos demonstrated cardiac edema, decreased heart rate, prolonged SV-BA distance, inhibited angiogenesis, and blocked blood circulation. Lenvatinib caused cardiac defects in the whole stage of cardiac development and increased the apoptosis of cardiomyocyte.Oxidative stress in the processed embryos was accumulated and inhibiting oxidative stress could rescue cardiac defects induced by lenvatinib. Additionally, we found that lenvatinib downregulated Notch signaling, and the activation of Notch signaling could rescue cardiac developmental defects and downregulate oxidative stress level induced by lenvatinib. Our results suggested that lenvatinib might induce cardiac developmental toxicity through inducing Notch mediated-oxidative stress generation, raising concerns about the harm of exposure to lenvatinib in aquatic organisms.

show abstract

“…In particular, hypertension is one of the most common adverse events associated with the use of TKIs, with an incidence of occurrence reported between 17% and 49.6% of patients [57]. Therefore, for those subjects already suffering from severe cardiovascular diseases, hypertension induced by TKIs could predispose to a higher risk of worsening of the condition and developing of cardiovascular events [57][58][59]. The molecular pathways involved in TKI-induced hypertension still need to be elucidated, and a genetic predisposition may be involved [57].…”

Section: Combination Therapy Versus Tki Alone In Selected Patient Subgroupsmentioning

confidence: 99%

Combination Therapy in Renal Cell Carcinoma: the Best Choice for Every Patient?

et al. 2021

View full text Add to dashboard Cite

Purpose of Review Therapeutic alternatives to treat metastatic renal cell carcinoma (mRCC) are increasing, and combination therapies, including antiangiogenic agents and tyrosine kinase/mTOR/immune checkpoint inhibitors, are identified as the gold standard driven by the results of recent clinical studies. Nevertheless, the real-world RCC population is very heterogeneous, with categories of patients not represented in the enrolled trial population who may not benefit more from these treatments. The purpose of this expert review is to assess the rationale on which tyrosine kinase alone may still be a viable first-line treatment option for some subgroups of patients with mRCC. Recent Findings The first-line treatment with tyrosine kinase inhibitor monotherapy can still be considered an effective tool for addressing selected mRCCs, as highlighted by the successful outcome in a range of subjects such as favorable-risk patients, the ones suffering from autoimmune diseases, those with pancreatic or lung metastases, or previously undergoing organ transplantation and elderly subjects. Summary Some selected categories of patients may still benefit from monotherapy with TKI, and smart sequential therapies can also be considered instead of a combination strategy. Tyrosine kinase inhibitors can also act as immune modulator agents, boosting the immune response to facilitate and potentiate the therapeutic effectiveness of subsequent immunotherapy.

show abstract

Cardiovascular Toxicities of Antiangiogenic Tyrosine Kinase Inhibitors: A Retrospective, Pharmacovigilance Study

Cited by 21 publications

References 45 publications

The Role of the VEGF Family in Atherosclerosis Development and Its Potential as Treatment Targets

The Role of the VEGF Family in Atherosclerosis Development and Its Potential as Treatment Targets

Lenvatinib induces cardiac developmental toxicity in zebrafish embryos through regulation of Notch mediated‐oxidative stress generation

Combination Therapy in Renal Cell Carcinoma: the Best Choice for Every Patient?

Contact Info

Product

Resources

About