Anthracycline- and HER2-induced cardiotoxicity: mechanisms, current strategies, and the emerging role of dapagliflozin as a targeted cardioprotective agent
Chemotherapy-induced cardiotoxicity (CIC) is a well-recognized and potentially severe complication of cancer treatment, particularly with... See more
Chemotherapy-induced cardiotoxicity (CIC) is a well-recognized and potentially severe complication of cancer treatment, particularly with anthracyclines and HER2-targeted therapies. As cancer survival improves, long-term cardiovascular outcomes have become increasingly important, yet current preventive strategies—such as dose reduction, dexrazoxane, neurohormonal blockers, and statins—offer only limited protection and are underutilized in routine clinical practice. There is a growing need for novel interventions that are safe, effective, and mechanistically targeted.
Dapagliflozin, a SGLT2 inhibitor initially developed for type 2 diabetes, has demonstrated substantial cardioprotective effects in patients with heart failure, regardless of glycemic status. Its mechanisms—including improved cardiac metabolism, mitochondrial preservation, anti-inflammatory and antioxidant effects, and inhibition of fibrosis—align closely with the known pathways of chemotherapy-induced myocardial injury. Preclinical models have shown that dapagliflozin can preserve left ventricular function, reduce biomarker elevation, and prevent structural remodeling in hearts exposed to doxorubicin.
Building on this evidence, a randomized, double-blind, placebo-controlled clinical trial (NCT06888505) is currently underway to evaluate dapagliflozin in cancer patients receiving anthracycline-based chemotherapy, with or without trastuzumab. The study incorporates serial biomarker assessments and cardiac function monitoring to assess its preventive potential.
Dapagliflozin represents a promising therapeutic candidate in cardio-oncology. Its pleiotropic cardioprotective effects, oral route of administration, and established safety profile make it a strong contender for integration into future preventive strategies aimed at reducing the cardiovascular burden of cancer therapy.
2025-11