In the Era of Cardiovascular–Kidney–Metabolic Syndrome in Cardio-Oncology: From Pathogenesis to Prevention and Therapy

Cardiovascular–kidney–metabolic (CKM) syndrome is a significant yet underrecognized condition in cancer patients, contributing to increased morbidity, reduced quality of life (QoL), and lower overall survival (OS). CKM syndrome arises from the interconnected pathophysiology of cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic dysfunction, which are further exacerbated by cancer therapies. Anticancer treatments such as anthracyclines, immune checkpoint inhibitors, tyrosine kinase inhibitors, and hormonal therapies can accelerate CKM progression by inducing cardiotoxicity, nephrotoxicity, and metabolic disturbances. To address these challenges, a multidisciplinary approach incorporating novel therapeutic strategies is essential. Emerging treatments include SGLT2i for their reno-cardiometabolic benefits, PCSK9i to reduce atherosclerotic cardiovascular disease (ASCVD) risk, and soluble guanylate cyclase activators for endothelial and cardiac function improvement. Additionally, dietary and lifestyle interventions play a crucial role in reduction of metabolic dysfunction and enhancing overall patient outcomes. By integrating these cardiometabolic therapies into oncology care, we can potentially improve OS, enhance QoL and reduce major adverse cardiovascular events (MACE) in cancer patients with CKM syndrome. Further clinical research is needed to optimize personalized strategies for CKM prevention and treatment in this high-risk population.