Possible Susceptibility Genes for Intervention against Chemotherapy-Induced Cardiotoxicity

Abstract

Recent therapeutic advances have significantly improved the short- and long-term survival rates in patients with heart disease and cancer. Survival in cancer patients may, however, be accompanied by disadvantages, namely, increased rates of cardiovascular events. Chemotherapy-related cardiac dysfunction is an important side effect of anticancer therapy. While advances in cancer treatment have increased patient survival, treatments are associated with cardiovascular complications, including heart failure (HF), arrhythmias, cardiac ischemia, valve disease, pericarditis, and fibrosis of the pericardium and myocardium. The molecular mechanisms of cardiotoxicity caused by cancer treatment have not yet been elucidated, and they may be both varied and complex. By identifying the functional genetic variations responsible for this toxicity, we may be able to improve our understanding of the potential mechanisms and pathways of treatment, paving the way for the development of new therapies to target these toxicities. Data from studies on genetic defects and pharmacological interventions have suggested that many molecules, primarily those regulating oxidative stress, inflammation, autophagy, apoptosis, and metabolism, contribute to the pathogenesis of cardiotoxicity induced by cancer treatment. Here, we review the progress of genetic research in illuminating the molecular mechanisms of cancer treatment-mediated cardiotoxicity and provide insights for the research and development of new therapies to treat or even prevent cardiotoxicity in patients undergoing cancer treatment. The current evidence is not clear about the role of pharmacogenomic screening of susceptible genes. Further studies need to done in chemotherapy-induced cardiotoxicity.

Prevalence of Hereditary Cancer Susceptibility Syndromes (HCSS) in Acute Lymphoblastic Leukemia (ALL): A Cross-Sectional Study in a Highly Consanguineous Population.

“…This is in concordance with the previous studies performed in highly consanguineous populations of Middle East that suggests that consanguinity confers protective effect to the development of the adult cancers at an early age (26)(27)(28). In the previous studies, different germ line genetic variations have been associated with the chemotherapy related cardiotoxicity (29,30). We also found that cardiotoxicity to be comparable in patients having family history of cancer when compared with patients without family history of cancer and it showed that the familial history of cancer asserts increase risk of toxicity in ALL patients (Table 3).…”

Cardiotoxic effect of bleomycin with a single administration in the experiment

“…Fragmentation of chromatin with its peripheral location was detected in some CMC nucleichromatin margination, which indicates apoptosis [9]. Destruction of nexuses of excessively shortened CMC is noted.…”

POLRMT as a Novel Susceptibility Gene for Cardiotoxicity in Epirubicin Treatment of Breast Cancer Patients

“…Several genetic variants have been associated with AIC, mainly in DOXtreated patients. Nevertheless, most of them have not been properly replicated [53][54][55]. This can be explained by the heterogeneity of the study designs, in which patients of different ages with different cancer types and/or treated with different anthracyclines were combined.…”