Reviewing the Path to Balance: Mechanisms and Management of Hypertension Associated with Targeting Vascular Endothelium in Cancer Therapy

Contemporary anticancer drugs are often accompanied by varying degrees of cardiovascular toxicity, with hypertension emerging as one of the most prevalent side effects, particularly linked to inhibitors of vascular endothelial growth factor receptor (VEGFR) and tyrosine kinase inhibitors (TKIs). Hypertension induced by cancer therapies contributes to increased cardiovascular mortality in cancer patients and survivors. Given the shared common risk factors and overlapping pathophysiological mechanisms, hypertension is also a prevalent comorbidity in this patient population. The mechanisms underlying hypertension induced by therapies targeting the vascular endothelial growth factor (VEGF) signaling pathway primarily involve reduced nitric oxide (NO) synthesis, increased endothelin-1 (ET-1) production, oxidative stress, microvascular rarefaction and dysfunction, decreased natriuresis, activation of the renin-angiotensin system (RAS), and partial endothelial cell death. Research into hypertension associated with therapies targeting the VEGF signaling pathway (VSP) could facilitate the optimization of cancer treatments, improve the evaluation and management of hypertension during targeted therapy, and help to reduce cardiovascular event rates and overall patient mortality. This review aims to provide a comprehensive summary of the current advancements in this area.