Objective:

To investigate the cardioprotective effects of dapagliflozin against sunitinib-induced cardiotoxicity and its mechanism of action, highlighting its potential significance in improving outcomes for RCC patients.

Key Findings:

• Sunitinib treatment induced significant cardiotoxicity characterized by left ventricular dysfunction and myocardial cell apoptosis, with specific metrics indicating the severity.
• Dapagliflozin effectively mitigated sunitinib-induced cardiotoxicity in both immunodeficient and immunocompetent mice, demonstrating its broad applicability.
• The cardioprotective effects of dapagliflozin were mediated through the AMPKα-PPARα pathway, enhancing mitochondrial function and reducing oxidative stress, with implications for therapeutic targeting.

Interpretation:

Dapagliflozin may serve as a therapeutic agent to reduce cardiotoxicity associated with sunitinib treatment in RCC patients, potentially improving patient outcomes and warranting further clinical exploration.

Limitations:

• The study was conducted in animal models, which may not fully replicate human responses, and potential biases in model selection should be considered.
• Further clinical studies are needed to validate the findings in human populations, particularly focusing on diverse patient demographics.

Conclusion:

Dapagliflozin shows promise in protecting against sunitinib-induced cardiotoxicity, warranting further investigation as a potential adjunct therapy in RCC treatment, with specific next steps for clinical trials suggested.