Cardiotoxicity of Anticancer Therapeutics

Abstract

As cancer therapeutics continues to improve and progress, the adverse side effects associated with anticancer treatments have also attracted more attention and have become extensively explored. Consequently, the importance of posttreatment follow-ups is becoming increasingly relevant to the discussion. Contemporary treatment methods, such as tyrosine kinase inhibitors, anthracycline chemotherapy, and immunotherapy regimens are effective in treating different modalities of cancers; however, these reagents act through interference with DNA replication or prevent DNA repair, causing endothelial dysfunction, generating reactive oxygen species, or eliciting non-specific immune responses. Therefore, cardiotoxic effects, such as hypertension, heart failure, and left ventricular dysfunction, arise posttreatment. Rising awareness of cardiovascular complications has led to meticulous attention for the evolution of treatment strategies and carefully monitoring between enhanced treatment effectiveness and minimization of adverse toxicity to the cardiovasculature, in which psychological assessments, early detection methods such as biomarkers, magnetic resonance imaging, and various drugs to reverse the damage from cardiotoxic events are more prevalent and their emphasis has increased tremendously. Fully understanding the mechanisms by which the risk factors action for various patients undergoing cancer treatment is also becoming more prevalent in preventing cardiotoxicity down the line.

MicroRNA‐129‐1‐3p protects cardiomyocytes from pirarubicin‐induced apoptosis by down‐regulating the GRIN2D‐mediated Ca2+ signalling pathway

“…Cardiovascular complications are common side effects of many anticancer therapies. 27 This is attributed to the highly interconnected nature of the molecular pathways regulating tumorigenesis and cardiac function. For example, constitutive activation of signal transducer and activator of transcription 3 (STAT3) promotes breast cancer progression through regulating Bcl-2, Bax, VEGF and MMP-7.…”

Rational Discovery of Dual-Action Multi-Target Kinase Inhibitor for Precision Anti-Cancer Therapy Using Structural Systems Pharmacology

“…In this study, we focus on searching for marked drugs that may act as a dual-action agent that can mitigate the cardiotoxicity of anti-cancer therapy, at the same time, present anti-cancer potency. Contemporary anti-cancer therapeutics, such as tyrosine kinase inhibitors, anthracycline chemotherapy, and immunotherapy, are all associated with the cardiotoxicity [12]. respectively.…”

Human Pluripotent Stem Cell-Derived Cardiomyocytes for Assessment of Anticancer Drug-Induced Cardiotoxicity

“…Although in recent years new anti-cancer therapies improved long-term survival rates, this is unfortunately also accompanied by an increased risk of cardiovascular complications because of adverse side effects of these anti-cancer drugs. Anthracyclines are a group of widely used anti-cancer drugs that are known to cause cardiac complications, either early or late after start of treatment (1)(2)(3)(4)(5)(6)(7). The history of anthracyclines originates in the 1950s when Daunorubicin was isolated from the bacteria Streptomyces peucetius.…”

“…In approximately 11% of patients, Doxorubicin-induced cardiotoxicity leads to an acute response within 2-3 days of administration (early onset of cardiotoxicity), manifested by chest pain resulting from different forms of arrhythmia (3). Chronic Doxorubicin-induced cardiomyopathy has a lower incidence (ranging from 4 to 36% dependent on the dose) and can occur as late as 10 years after the last dose (late onset of chronic cardiotoxicity), with only a 50% 1-year survival prognosis when cardiomyopathy further develops into congestive heart failure (3,7). Importantly, anthracycline-induced cardiotoxicity endangers cancer patients since the early 70s (9,10).…”