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Sex differences in cardiomyocyte proteomic responses to the cardiotoxic chemotherapy drug doxorubicin

Dozic, S.; Leeming, M. G.; Datta, K. K.; Kore, H.; Howden, E. J.; Parker, B. L.; Delbridge, L. M. D.; Weeks, K. L.

2026-04-24 molecular biology
10.64898/2026.04.21.715711 bioRxiv
Show abstract

Anthracyclines, including doxorubicin, are widely used chemotherapeutic agents, but dose-dependent cardiotoxicity limits their clinical utility and increases the risk of heart failure in cancer survivors. In paediatric patients, female sex is a significant risk factor for anthracycline-associated cardiotoxicity, yet pre-clinical studies rarely investigate sex differences in immature hearts. Here, we provide a proteomic dataset from primary cardiomyocytes, isolated from postnatal day 2 rat hearts and treated with a clinically relevant concentration of doxorubicin. Analysis of proteins present in all samples identified candidates previously shown to be regulated by doxorubicin in adult hearts, as well as candidates that may be specifically regulated in young hearts. This dataset provides a resource for generating hypotheses on molecular mechanisms contributing to sex differences in juvenile doxorubicin-induced cardiotoxicity.

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