Cardiotoxicity of Anticancer Drugs: Molecular Mechanisms, Clinical Management and Innovative Treatment

Abstract

With the continuous refinement of therapeutic measures, the survival rate of tumor patients has been improving year by year, while cardiovascular complications related to cancer therapy have become increasingly prominent. Exploring the mechanism and prevention strategy of cancer therapy-related cardiovascular toxicity (CTR-CVT) remains one of the research hotspots in the field of Cardio-Oncology in recent years. Cardiotoxicity of anticancer drugs involves heart failure, myocarditis, hypertension, arrhythmias and vascular toxicity, mechanistically related to vascular endothelial dysfunction, ferroptosis, mitochondrial dysfunction and oxidative stress. To address the cardiotoxicity induced by different anticancer drugs, various therapeutic measures have been put in place, such as reducing the accumulation of anticancer drugs, shifting to drugs with less cardiotoxicity, using cardioprotective drugs, and early detection. Due to the very limited treatments available to ameliorate anticancer drugs-induced cardiotoxicity, a few innovations are being shifted from animal studies to human studies. Examples include mitochondrial transplantation. Mitochondrial transplantation has been proven to be effective in in vivo and in vitro experiments. Several recent studies have demonstrated that intercellular mitochondrial transfer can ameliorate doxorubicin(DOX)-induced cardiotoxicity, laying the foundation for innovative therapies in anticancer drugs-induced cardiotoxicity. In this review, we will discuss the current status of anticancer drugs-induced cardiotoxicity in terms of the pathogenesis and treatment, with a focus on mitochondrial transplantation, and we hope that this review will bring some inspiration to you.

Keywords: CTR-CVT; cancer therapy-related cardiovascular toxicity; ferroptosis; mitochondrial dysfunction; mitochondrial transplantation; oxidative stress.

Graphical abstract

Figure 1

Pathogenesis of doxorubicin-induced cardiotoxicity. DOX can disrupt intracellular Ca²⁺ homeostasis, open the mPTP and release apoptotic signalling molecules such as CytC. DOX can disrupt the structure of mitochondria, producing ROS that exacerbates mitochondrial dysfunction. Doxorubicin can inhibit the function of the mitochondrial ETC and reduce the level of ATP in cardiomyocytes. DOX can accumulate in mtDNA,leading to the development of ferroptosis. DOX can bind to topoisomerase 2β and disrupt the DNA double strand, leading to apoptosis of cardiomyocytes. By Figdraw.

Figure 2

Mitochondrial transplantation and doxorubicin-induced cardiotoxicity. Doxorubicin--induced cardiotoxicity is closely related to mitochondrial dysfunction, oxidative stress,ferroptosis. Mitochondrial transplantation can alleviate ferroptosis by enhancing mitochondrial function, reducing reactive oxygen species production. By Figdraw.

Figure 3

The process of mitochondrial transplantation and the protective mechanisms of mitochondrial transplantation. Mitochondria from different tissues or cells are transferred in different ways to dysfunctional tissues or cells to improve their function. By Figdraw.