Can short-term fasting protect against doxorubicin-induced cardiotoxicity?

Abstract

Doxorubicin (Dox) is one of the most effective chemotherapeutic agents used in the treatment of several types of cancer. However the use is limited by cardiotoxicity. Despite extensive investigation into the mechanisms of toxicity and preventative strategies, Dox-induced cardiotoxicity still remains a major cause of morbidity and mortality in cancer survivors. Thus, continued research into preventative strategies is vital. Short-term fasting has proven to be cardioprotective against a variety of insults. Despite the potential, only a few studies have been conducted investigating its ability to prevent Dox-induced cardiotoxicity. However, all show proof-of-principle that short-term fasting is cardioprotective against Dox. Fasting affects a plethora of cellular processes making it difficult to discern the mechanism(s) translating fasting to cardioprotection, but may involve suppression of insulin and insulin-like growth factor-1 signaling with stimulated autophagy. It is likely that additional mechanisms also contribute. Importantly, the literature suggests that fasting may enhance the antitumor activity of Dox. Thus, fasting is a regimen that warrants further investigation as a potential strategy to prevent Dox-induced cardiotoxicity. Future research should aim to determine the optimal regimen of fasting, confirmation that this regimen does not interfere with the antitumor properties of Dox, as well as the underlying mechanisms exerting the cardioprotective effects.

Keywords: Fasting; Doxorubicin; Cardiotoxicity; Cardioprotection

Core tip: Doxorubicin (Dox)-induced cardiotoxicity remains a significant cause of morbidity and mortality in cancer survivors, despite the intensive investigation of potential protective strategies. Studies have shown that short-term fasting induces cardioprotective effects against Dox-induced injury. Importantly, evidence suggests that fasting may enhance the antitumor effects of Dox. Thus, short-term fasting may be a feasible practice that can easily be incorporated into the treatment plans of cancer patients.