Recent Advances on the Molecular Mechanism and Prevention of Cardiotoxicity Induced in Targeted Cancer Therapy

Review Article

Austin Cardio & Cardiovasc Case Rep. 2022; 7(1): 1048.

Recent Advances on the Molecular Mechanism and Prevention of Cardiotoxicity Induced in Targeted Cancer Therapy

Guo X1#, Jin Y2#, Qian X1#, Chen J1, Wang S1, Bai X1, Wu C1* and Li W2*

¹Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, China

²Department of Cardiology, Xiamen Key Laboratory of Cardiac Electrophysiology, Xiamen Institute of Cardiovascular Diseases, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, China

#These authors are contributed equally to this article

*Corresponding author: Caisheng Wu, Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen, 361102, China

Weihua Li, Department of Cardiology, Xiamen Key Laboratory of Cardiac Electrophysiology, Xiamen Institute of Cardiovascular Diseases, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361003, China

Received: August 08, 2022; Accepted: August 30, 2022; Published: September 06, 2022

Abstract

First proposed in 2000, cardio-oncology bears the mission to reduce cardiotoxicity whilst successfully treating cancer. Through two decades of development, substantial progress had been made in determining the specific clinical symptoms, mechanism of action, ways of monitoring, and toxicity reduction of the cardiotoxicity induced by cancer-related treatment. By summarizing the progress in cardiotoxicity induced by targeted cancer therapy in the past two decades, this mini-review aims to give some enlightenment on the fundamental research of cardio-oncology.

Keywords: Cancer treatment; Cardiotoxicity; Mechanism of action; Way of monitoring; Prevention strategy

Abbreviations

ABL: Abelson; Ang II: Angiotensin II; APC: Antigen Presenting Cells; ASK1: Apoptosis Signal-Regulating Kinase 1; ATP: Adenine Triphosphate; Bcl-2: B-Cell Lymphoma-2; BNP: Brain Natriuretic Peptide; CTLA-4: Cytotoxic T Lymphocyte-Associated Antigen-4; eNOS: Endothelial Nitric Oxide Synthase; ESC: European Society of Cardiology; HER-2: Human Epidermal Growth Factor Receptor-2; HER-4: Human Epidermal Growth Factor Receptor-4; Iodine 123- mIBG: meta-Iodobenzyl Guanidine; IRE-1: Inositol-Requiring Enzyme-1; JNK: c-Jun N-Terminal Kinase; LVD: Left Ventricular Dysfunction; LVEF: Left Ventricular Ejection Fraction; MRI: Magnetic Resonance Imaging; NO: Nitric Oxide; NRG-1: Neuregulin-1; NTpro BNP: N-terminal pro-Brain Natriuretic Peptide; PDGF: Platelet- Derived Growth Factor; PD-L1: Programmed Cell Death 1 Ligand 1; PGI2: Prostaglandin I; PP2A: Protein Phosphatase 2 A; ROS: Reactive Oxygen Species; TKI: Tyrosine Kinase Inhibitor; Tn: Troponin; UCG: Ultrasonic Cardiogram; VEGF: Vascular Endothelial Growth Factor

Introduction

Cancer has always been a major obstacle on the road to human health, and in addition to surgery, chemotherapy, and radiation therapy, novel treatment methods have emerged, such as molecular targeted drug therapy, immunotherapy and so on. Thanks to these diverse treatments, cancer patients are surviving and the survival rates increase steadily. Relatively, however, surviving cancer patients are almost accompanied by heart disease.

As cardiotoxicity induced by cancer-related treatment is gaining more attention, the oncology and cardiology, as two traditionally separate disciplines, gradually integrate into one emerging science in clinical practice. More interestingly, this novel science field has been named as cardio-oncology [1,2], which takes the cardiovascular diseases of patients suffering from malignant tumors, undergoing anti-cancer treatment, or having history of cancer as the research subjects [3]. Not limited to identification and detection of cancer treatment-related cardiovascular diseases, cardio-oncology also sets out to classify patients undergoing anti-cancer treatment as per their risks, to diagnose and deal with the resulting cardiotoxicity, and to trace both short-term or long-term cardiac symptoms during or after cancer treatment [1,3]. The ultimate goal of cardio-oncology is to protect the heart while treating cancer [4].

As revealed by ESC proposal concerning anticancer treatment and cardiotoxicity in 2016, the cardiotoxicity related to anticancer treatment can be divided into nine categories: cardiac insufficiency, arrhythmia, heart valve disease, coronary artery disease, thrombosis, hypertension, pulmonary arterial hypertension, peripheral vascular diseases and stroke, and other cardiovascular complications [5]. The cardiotoxicity of anticancer treatment means other cardiovascular diseases, which are induced in interfering with or removing the cancer cells in patients’ bodies. Given the increasing cancer survival rate, the studies on cardiotoxicity induced by cancer-related treatment turn to be more and more important. Cancer and cardiovascular diseases share some common risk factors (e.g., age, smoking, alcohol, obesity, sedentariness, diabetes and hypertension), so most cancer patients have clinical or subclinical heart diseases when receiving cancer diagnosis and treatment. Consequently, the therapies containing chemotherapeutic drugs and targeted drugs usually have to be suspended and the patients canonly settle for other suboptimal schemes [6].

Cardio-oncology has made a lot of research progress in the relationship between cancer and heart disease in past two decades. Many scholars have summarized the underlying cardiotoxicity of targeted cancertherapy,but most of them focus on the clinical perspective, and there is a lack of discussion on the specific mechanism of cardiotoxicity induced by targeted drugs. This mini-review places special emphasis on the mechanism of cardiotoxicity and discuss the methods of preventing cardiotoxicity and is hoped that it could shed light on the clinical treatment of cancer and the prevention of cardiotoxicity.

Mechanism of Cardiotoxicity Induced by Targeted Drugs

Targeted drugs underwent a development by leaps and bounds during the last decade. Exerting treatment on specific targeted sites, targeted agents are theoretically safer than traditional chemotherapies. Nevertheless, present clinical practice indicates targeted agents are also perplexed by extensive cardiotoxicity (Table 1). The following is a summary of the mechanism of cardiotoxicity induced by targeted drugs (Figure 1).

Citation: Guo X, Jin Y, Qian X, Chen J, Wang S, Bai X, et al. Recent Advances on the Molecular Mechanism and Prevention of Cardiotoxicity Induced in Targeted Cancer Therapy. Austin Cardio & Cardiovasc Case Rep. 2022; 7(1): 1048.