Doxorubicin-Induced Cardiotoxicity: A Comprehensive Update

Abstract

Doxorubicin is an anthracycline chemotherapeutic that is widely used for treating various malignancies, including breast cancer, lymphomas, and sarcomas. Despite its efficacy, its clinical utility is limited by a well-documented risk of cardiotoxicity, which may manifest acutely or chronically. Doxorubicin works by intercalating DNA and inhibiting topoisomerase II, leading to DNA damage and cell death. However, this mechanism is not selective to cancer cells and can adversely affect cardiac myocytes. The introduction of doxorubicin into oncologic practice has revolutionized cancer treatment, but its cardiotoxic effects remain a significant concern. This systematic review aims to comprehensively examine the multifaceted impact of doxorubicin on cardiac structure and function through both preclinical and clinical lenses.

Keywords: DNA damage; anthracyclines; cardiomyopathy; cell death; doxorubicin; heart failure; oncology.

Figure 1

Accumulation of doxorubicin metabolites in the heart enhances oxidative stress via increased production of reactive oxygen species and mitochondrial dysfunction. These mechanisms can ultimately lead to cardiomyocyte injury, cardiac adverse remodeling, and, eventually, heart failure.

Figure 2

Future management of doxorubicin-induced cardiac injury. Forthcoming research and clinical strategies should prioritize the development of safe alternative drug therapies, integrated cardioprotective care models such as cardio-oncology, and personalized prevention and treatment pathways for patients.