Cardiotoxicity in Childhood Cancer Survivors: Strategies for Prevention and Management

Abstract

Advances in cancer treatment have greatly improved survival rates of children with cancer. However, these same chemotherapeutic or radiologic treatments may result in long-term health consequences. Anthracyclines, chemotherapeutic drugs commonly used to treat children with cancer, are known to be cardiotoxic, but the mechanism by which they induce cardiac damage is still not fully understood. A higher cumulative anthracycline dose and a younger age of diagnosis are only a few of the many risk factors that identify the children at increased risk of developing cardiotoxicity. While cardiotoxicity can develop at anytime, starting from treatment initiation and well into adulthood, identifying the best cardioprotective measures to minimize the long-term damage caused by anthracyclines in children is imperative. Dexrazoxane is the only known agent to date, that is associated with less cardiac dysfunction, without reducing the oncologic efficacy of the anthracycline doxorubicin in children. Given the serious long-term health consequences of cancer treatments on survivors of childhood cancers, it is essential to investigate new approaches to improving the safety of cancer treatments.

Acute adriamycin-induced cardiotoxicity is exacerbated by angiotension II

“…In addition, mitochondrial damage, increased Ca 2? current along with inhibition of sarcoplasmic reticulum function and decreased activity of Na, K-ATPase, have all been implicated in ADR-induced cardiotoxicity (Harake et al 2012).…”

“…ADR is shown to accumulate in mitochondria which produce more than 90 % of the ATP utilized by cardiomyocytes (Octavia et al 2012). Cationic ADR has high affinity binding to cardiolipin, an anionic phospholipid in the inner mitochondrial membrane, which is essential in eukaryotic energy metabolism (Harake et al 2012). Cardiolipin-bound ADR would induce dissociation of cardiolipin-associated peripheral proteins from the inner mitochondrial membrane, like cytochrome c. This would affect electron transport chain and energy channeling, and may favor initiation of programmed cell death (Harake et al 2012).…”

Modulatory Effects of Dexrazoxane Against Genotoxicity and Lipid Peroxidation Induced by Idarubicin in HepG2 Cells

“…DNA damage and degradation of protein and lipids, and is mainly accepted as one of the most important risk factors in the development of chronic diseases (41). Another result of free radical generation is lipid peroxidation, which is believed to be one of the causes of cardiovascular disease and cancer (42). The lipid peroxidation products mostly react with DNA, showing both genotoxic and mutagenic action.…”

The use of biomarkers in detecting subclinical cardiotoxicity in doxorubicin-based treatment for paediatric patients with acute lymphoblastic leukaemia

“…Chemotherapy-induced cardiotoxicity can be divided into three categories: acute, early and late-onset progressive cardiomyopathy [1].…”

“…The second form occurs during the first year after treatment in 1.6-2.1%, while the third type develops after this period. It is estimated that 65% of cancer survivors present signs of cardiac damage 6 years after treatment [1].…”