Harnessing Ultrasound for Tumor Vascular Targeting: From Mechanistic Insights to Clinical Monitoring and Therapeutic Applications

The tumor vasculature, characterized by pathological angiogenesis and structural abnormalities, drives the progression of solid tumors by inducing hypoxia-acidosis microenvironments and therapeutic resistance. Targeting the tumor vasculature has emerged as a critical therapeutic strategy. Although conventional approaches such as anti-angiogenic drugs, vascular disrupting agents, and embolization have shown efficacy, their single-target focus hinders addressing tumor heterogeneity and evolving stage-specific needs. For example, rapid vascular disruption is effective for debulking advanced tumors, whereas vascular normalization enhances early- to mid-stage therapy by improving postoperative chemo-radiotherapy outcomes. Unlike single-mechanism interventions, ultrasound modulates acoustic parameters to achieve diverse effects including angiogenesis suppression, vessel disruption, and vasodilation, thus addressing multi-stage vascular needs. Ultrasound-based monitoring systems provide precise, dynamic vascular assessments to guide intervention strategies. Compared with traditional static imaging ultrasound offers real-time angiogenesis visualization and therapeutic response evaluation, thus enabling treatment optimization. This review synthesizes recent advances in ultrasound-based vascular targeting, emphasizing its dual role in spatiotemporally adaptive therapy and angiogenesis monitoring. We critically examine clinical translation challenges and future directions, highlighting how ultrasound-driven strategies, by bridging mechanistic precision with clinical scalability, might enable personalized, multi-effect therapeutic paradigms in oncology.