Cardiotoxicity of BRAF/MEK inhibitors

Rapidly accelerated fibrosarcoma type B/B-Raf proto-oncogene, serine/threonine kinase (BRAF) and mitogen-activated protein kinase (MEK) inhibitors have transformed outcomes in cancer therapy, particularly in melanoma. However, cardiovascular toxicities are increasingly recognized in real-world clinical practice. Reported events include asymptomatic left ventricular ejection fraction decline and heart failure, hypertension, venous and arterial thromboembolism, QT prolongation or arrhythmias. The underlying mechanisms are multifactorial, involving on-target disturbances of extracellular signal-regulated kinase signalling in cardiomyocytes and endothelium, off-target mitochondrial and metabolic effects, microvascular dysfunction and inflammation, with risk patterns differing between combination therapy and monotherapy. This review synthesizes the biological rationale of BRAF and MEK inhibitors, summarizes incidence and phenotype of cardiotoxicity across pivotal trials and observational cohorts, outlines baseline risk assessment and surveillance strategies and proposes pragmatic management algorithms aligned with contemporary cardio-oncology guidance. Understanding, detecting, and managing cardiotoxicity proactively enables safe delivery of highly effective BRAF/MEK-directed therapy while preserving cardiovascular health.