Systematic review of metabolomics approaches in identifying biomarkers of chemotherapy-induced cardiotoxicity among breast cancer patients

Background: While anthracyclines are well known to cause cardiotoxicity, no validated biomarkers that can predict the early development of anthracycline-induced cardiotoxicity (AIC) currently exist. Therefore, early biomarkers of AIC are urgently needed. Metabolomics approaches have been used to elucidate this relationship. However, differences in pre-clinical model systems making it challenging to draw conclusions from the discoveries and translate into clinical development. Aim: of Review. A systematic literature review on metabolomics studies of AIC in breast cancer was conducted with the goal to identify and compare study results reported using cell culture models, animal models, tumor-bearing animal models, and clinical patients. We further pooled metabolites identified from all studies to identify biologically meaningful patterns that are significantly enriched in the data. Lastly, pooled metabolites perturbed by AIC were mapped to metabolic pathways for potential pathological implications. Key Scientific Concepts of Review. Altogether, metabolomics studies suggest metabolic alterations in AIC, albeit little overlap between studies especially with breast cancer patients. Attempts at intercepting these pathways have shown that intervention in AIC may be possible. Optimal study design to accurately mimic the human breast cancer condition taking cancer metabolism into consideration will play key role to translate animal models to clinical studies to identify biomarkers in the early diagnosis of AIC and point to new targets for intervention.