Deciphering the Role of AMPK in Doxorubicin Cardiotoxicity

This NIH-funded research project is focused on preventing long-term cardiac damage caused by the widely used anticancer drug doxorubicin (DOX). DOX is highly effective across many cancers but carries a significant risk of cardiotoxicity that can lead to heart failure, posing lifelong health challenges for millions of cancer survivors. Liang’s project, supported by a $428,400 award from the National Heart, Lung and Blood Institute, aims to uncover strategies that reduce DOX’s harmful effects on the heart while preserving its antitumor efficacy.

The research team will reproduce and analyze DOX cardiotoxicity in both cultured cardiac myocytes and animal models. Through these preclinical systems, they will characterize the cellular and molecular signaling pathways that mediate DOX-induced myocyte death and cardiac dysfunction. By identifying key signaling events that link DOX exposure to cardiomyocyte injury, the project seeks to reveal targets and interventions that can mitigate heart damage without diminishing the drug’s cancer-killing properties.

The investigation emphasizes rigorous mechanistic study and translational potential. Work in cultured heart muscle cells allows for controlled dissection of pathways and direct observation of DOX effects on myocyte viability. Complementary animal model studies enable assessment of cardiac structure and function in the context of whole-organism physiology, providing a bridge toward clinically relevant interventions. Together, these approaches aim to generate robust preclinical evidence to support the development of cardioprotective strategies that can be integrated into cancer treatment regimens.

If successful, this work could inform new therapeutic approaches that allow oncologists to use DOX and similar agents more safely, preserving life-saving anticancer activity while reducing the burden of cardiovascular disease in cancer survivors. The research aligns scientific inquiry with practical clinical significance and educational mission, advancing both knowledge about DOX cardiotoxicity and the training of future clinician-scientists who will carry these advances toward improved patient care.