» Articles » PMID: 33530139

Targeting Endothelial Cell Metabolism for Cardio-protection from the Toxicity of Antitumor Agents

Overview
Journal Cardiooncology
Publisher Biomed Central
Specialty Oncology
Date 2021 Feb 3
PMID 33530139
Citations 12
Authors
Affiliations
Soon will be listed here.
Abstract

The vascular endothelium plays a fundamental role in the maintenance of tissue homeostasis, regulating local blood flow and other physiological processes. Chemotherapeutic drugs and target therapies, including antiangiogenic drugs targeting vascular endothelial growth factor (VEGF) or its receptors, not only efficiently act against tumor growth, but may also induce endothelial dysfunction and cardiovascular toxicity. Continued research efforts aim to better understand, prevent and mitigate these chemotherapy associated cardiovascular diseases. Conventional chemotherapeutic agents, such as anthracyclines, platinum compounds, and taxanes, and newer targeted agents, such as bevacizumab, trastuzumab, and tyrosine kinase inhibitors, have known risk of cardiovascular toxicity, which can limit their effectiveness by promoting increased morbidity and/or mortality. This review describes a) the activity of anticancer agents in inducing endothelial dysfunction, b) the metabolic pathways and signalling cascades which may be targeted by protective agents able to maintain or restore endothelial cell function, such as endothelial nitric oxide synthase/fibroblast growth factor-2 (eNOS-FGF-2) pathway, and c) the drugs/strategies reported to improve endothelial function and to reduce the risks of cardiovascular diseases such as angiotensin converting enzyme inhibitors (ACEi) and beta blockers, that are fundamental therapies in chronic heart failure (HF), as well as non-standard HF treatments such ad nitric oxide donors and antioxidant strategies. There is increasing interest in whether ACEi, beta-blockers, and/or statins might prevent and/or therapeutically control cardiotoxic effects in cancer patients. Maintaining endothelial function during or following treatments with chemotherapeutic agents, without affecting anti-tumor drug-effectiveness, is essential for preserving or recovering cardiovascular homeostasis. In this respect, the early detection and immediate therapy of cardiovascular toxicity appear crucial for substantial recovery of cardiac function in cancer patients.

Citing Articles

Research Progress on Flavonoids in Traditional Chinese Medicine to Counteract Cardiotoxicity Associated with Anti-Tumor Drugs.

Shi H, Duan L, Tong L, Pu P, Wei L, Wang L Rev Cardiovasc Med. 2024; 25(3):74.

PMID: 39076949 PMC: 11263839. DOI: 10.31083/j.rcm2503074.


Early detection of the impact of combined taxane and carboplatin treatment on autonomic nerves in patients with cervical cancer: Measurement of heart rate variability.

Liu J, Guan W, Sun Y, Wang Y, Li G, Zhang S Front Physiol. 2023; 14:1126057.

PMID: 36926192 PMC: 10011481. DOI: 10.3389/fphys.2023.1126057.


Posterior reversible encephalopathy syndrome after anlotinib treatment for small cell lung cancer: A case report and literature review.

Zou X, Zhou P, Lv W, Liu C, Liu J Front Pharmacol. 2023; 14:1126235.

PMID: 36814495 PMC: 9939648. DOI: 10.3389/fphar.2023.1126235.


Pharmaceutical Prevention and Management of Cardiotoxicity in Hematological Malignancies.

Perpinia A, Kadoglou N, Vardaka M, Gkortzolidis G, Karavidas A, Marinakis T Pharmaceuticals (Basel). 2022; 15(8).

PMID: 36015155 PMC: 9412591. DOI: 10.3390/ph15081007.


Updates on Anticancer Therapy-Mediated Vascular Toxicity and New Horizons in Therapeutic Strategies.

Hsu P, Mammadova A, Benkirane-Jessel N, Desaubry L, Nebigil C Front Cardiovasc Med. 2021; 8:694711.

PMID: 34386529 PMC: 8353082. DOI: 10.3389/fcvm.2021.694711.


References
1.
Bozcali E, Dedeoglu D, Karpuz V, Suzer O, Karpuz H . Cardioprotective effects of zofenopril, enalapril and valsartan against ischaemia/reperfusion injury as well as doxorubicin cardiotoxicity. Acta Cardiol. 2012; 67(1):87-96. DOI: 10.1080/ac.67.1.2146570. View

2.
Tewey K, Rowe T, Yang L, Halligan B, Liu L . Adriamycin-induced DNA damage mediated by mammalian DNA topoisomerase II. Science. 1984; 226(4673):466-8. DOI: 10.1126/science.6093249. View

3.
Swain S, Whaley F, Ewer M . Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer. 2003; 97(11):2869-79. DOI: 10.1002/cncr.11407. View

4.
Hotchkiss K, Ashton A, Mahmood R, Russell R, Sparano J, Schwartz E . Inhibition of endothelial cell function in vitro and angiogenesis in vivo by docetaxel (Taxotere): association with impaired repositioning of the microtubule organizing center. Mol Cancer Ther. 2002; 1(13):1191-200. View

5.
Colombo A, Cipolla C, Beggiato M, Cardinale D . Cardiac toxicity of anticancer agents. Curr Cardiol Rep. 2013; 15(5):362. DOI: 10.1007/s11886-013-0362-6. View