Combination of vascular surgery with novel vascular targeting agents as cancer therapeutics

Locally advanced solid tumors, characterized by complex involvement or encasement of major vascular structures, present a significant challenge in curative oncology. Achieving microscopically negative margins often mandates extensive surgical procedures, collectively termed Oncovascular Surgery (OVS). While OVS successfully addresses the anatomical barrier to resection, the resulting surgical trauma is intrinsically linked to an acute systemic release of pro-angiogenic factors, frequently correlating with accelerated tumor recurrence and metastatic potential. Novel Vascular Targeting Agents (VTAs) offer critical pharmacological control over the tumor vasculature. These agents are categorized primarily into Anti-Angiogenic Agents (AIAs), which inhibit new vessel growth, and Vascular Disrupting Agents (VDAs), which induce rapid collapse of established tumor blood vessels. The clinical integration of mechanical clearance (OVS) with strategic pharmacological control (VTA administration) is highly complex, demanding precise timing and toxicity management. This review synthesizes the molecular mechanisms underpinning VTA function and selectivity, details the technical necessity and consequences of OVS, and critically evaluates the biological interface including mechanisms of resistance and the systemic post-surgical angiogenic surge to establish a unified translational strategy for synergistic combination regimens.