0000000000160742
AUTHOR
Paolo Spallarossa
Cardioprotection by gene therapy
Ischemic heart disease remains the leading cause of death worldwide. Ischemic pre-, post-, and remote conditionings trigger endogenous cardioprotection that renders the heart resistant to ischemic-reperfusion injury (IRI). Mimicking endogenous cardioprotection by modulating genes involved in cardioprotective signal transduction provides an opportunity to reproduce endogenous cardioprotection with better possibilities of translation into the clinical setting. Genes and signaling pathways by which conditioning maneuvers exert their effects on the heart are partially understood. This is due to the targeted approach that allowed identifying one or a few genes associated with IRI and cardioprote…
Redox imbalances in ageing and metabolic alterations: Implications in cancer and cardiac diseases. An overview from the working group of cardiotoxicity and cardioprotection of the Italian society of cardiology (SIC)
Metabolic syndrome (MetS) is a well established risk factor for cardiovascular (CV) diseases. In addition, several studies indicate that MetS correlates with the increased risk of cancer in adults. The mechanisms linking MetS and cancer are not fully understood. Several risk factors involved in MetS are also cancer risk factors, such as the consumption of high calorie-food or high fat intake, low fibre intake, and sedentary lifestyle. Other common aspects of both cancer and MetS are oxidative stress and inflammation. In addition, some anticancer treatments can induce cardiotoxicity, including, for instance, left ventricular (LV) dysfunction and heart failure (HF), endothelial dysfunction an…
A recommended practical approach to the management of target therapy and angiogenesis inhibitors cardiotoxicity: an opinion paper of the working group on drug cardiotoxicity and cardioprotection, Italian Society of Cardiology.
The US National Cancer Institute estimates that cardiotoxicity (CTX) from target therapy refers mostly to four groups of drugs: epidermal growth factor receptor 2 inhibitors, angiogenic inhibitors, directed Abelson murine leukemia viral oncogene homolog inhibitors, and proteasome inhibitors. The main cardiotoxic side-effects related to antiepidermal growth factor receptor 2 therapy are left ventricular systolic dysfunction and heart failure. Angiogenesis inhibitors are associated with hypertension, left ventricular dysfunction/heart failure, myocardial ischemia, QT prolongation, and thrombosis. Moreover, other agents may be related to CTX induced by treatment. In this study, we review the g…
A recommended practical approach to the management of anthracycline-based chemotherapy cardiotoxicity: an opinion paper of the working group on drug cardiotoxicity and cardioprotection, Italian Society of Cardiology.
Anthracyclines are the mainstay of treatment of a variety of haematological malignancies and solid tumours. Unfortunately, the clinical use of these drugs is limited by cumulative, dose-related cardiotoxicity which may ultimately lead to a severe and irreversible form of cardiomyopathy. Thus, there is an increasing need for close cooperation among cardiologists, oncologists and haemato-oncologists. As anthracyclines save lives, the logical goal of this cooperation, besides preventing or mitigating cardiotoxicity, is to promote an acceptable balance between the potential cardiac side effects and the vital benefit of anticancer treatment. This manuscript, which is specifically addressed to th…
Improving the preclinical models for the study of chemotherapy-induced cardiotoxicity: a Position Paper of the Italian Working Group on Drug Cardiotoxicity and Cardioprotection
Although treatment for heart failure induced by cancer therapy has improved in recent years, the prevalence of cardiomyopathy due to antineoplastic therapy remains significant worldwide. In addition to traditional mediators of myocardial damage, such as reactive oxygen species, new pathways and target cells should be considered responsible for the impairment of cardiac function during anticancer treatment. Accordingly, there is a need to develop novel therapeutic strategies to protect the heart from pharmacologic injury, and improve clinical outcomes in cancer patients. The development of novel protective therapies requires testing putative therapeutic strategies in appropriate animal model…
Anthracyclines and regional myocardial damage in breast cancer patients. A multicentre study from the Working Group on Drug Cardiotoxicity and Cardioprotection, Italian Society of Cardiology (SIC)
Abstract Aims In breast cancer (BC) patients treated with anthracyclines-based therapies, we aim at assessing whether adjuvant drugs impact cardiac function differently and whether their cardiotoxicity has a regional pattern. Methods and results In a multicentre study, 146 BC patients (56 ± 11 years) were prospectively enrolled and divided into three groups according to the received treatments: AC/EC-Group (doxorubicin or epirubicin + cyclophosphamide), AC/EC/Tax-Group (AC/EC + taxanes), FEC/Tax-Group (fluorouracil + EC + taxanes). Fifty-six patients of the total cohort also received trastuzumab. Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were calculated …
Arterial hypertension in cancer: The elephant in the room
The great therapeutical success achieved by oncology is counterbalanced by growing evidences of cardiovascular (CV) toxicity due to many antineoplastic treatments. Cardiac adverse events may cause premature discontinuation of effective oncologic treatments or occur as late events undermining the oncologic success. Arterial hypertension is both the most common comorbidity in cancer patients and a frequent adverse effect of anticancer therapies. A pre-existing hypertension is known to increase the risk of other cardiac adverse events due to oncologic treatments, in particular heart failure. Moreover, as a strict association between cancer and CV diseases has emerged over the recent years, var…
Antineoplastic Drug-Induced Cardiotoxicity: A Redox Perspective
Antineoplastic drugs can be associated with several side effects, including cardiovascular toxicity (CTX). Biochemical studies have identified multiple mechanisms of CTX. Chemoterapeutic agents can alter redox homeostasis by increasing the production of reactive oxygen species (ROS) and reactive nitrogen species RNS. Cellular sources of ROS/RNS are cardiomyocytes, endothelial cells, stromal and inflammatory cells in the heart. Mitochondria, peroxisomes and other subcellular components are central hubs that control redox homeostasis. Mitochondria are central targets for antineoplastic drug-induced CTX. Understanding the mechanisms of CTX is fundamental for effective cardioprotection, without…
Pathophysiology of anthracycline cardiotoxicity.
Anthracyclines (ANTs) are powerful drugs that have reduced the mortality of cancer patients. However, their use is limited by the development of cardiotoxicity (CTX), which is dose dependent and may lead to left ventricular dysfunction and heart failure. Although various strategies have been suggested to reduce the negative effects of ANTs, CTX is still an important unresolved clinical issue. This may be due at least partly to the incomplete characterization of the molecular and cellular mechanisms of ANT-induced CTX. In addition, although various forms of cardiac damage have been demonstrated with the use of these drugs in experimental studies, it is not yet clear how these translate to th…
From molecular mechanisms to clinical management of antineoplastic drug-induced cardiovascular toxicity: A translational overview
Significance: Antineoplastic therapies have significantly improved the prognosis of oncology patients. However, these treatments can bring to a higher incidence of side-effects, including the worrying cardiovascular toxicity (CTX). Recent Advances: Substantial evidence indicates multiple mechanisms of CTX, with redox mechanisms playing a key role. Recent data singled out mitochondria as key targets for antineoplastic drug-induced CTX; understanding the underlying mechanisms is, therefore, crucial for effective cardioprotection, without compromising the efficacy of anti-cancer treatments. Critical Issues: CTX can occur within a few days or many years after treatment. Type I CTX is associated…