Vascular plasticity in the gastric cancer environment: mechanisms, prognostic significance, and concepts of therapeutic interventions

Abstract

Gastric cancer (GC) remains a major global health problem because of its aggressive behavior and frequent development of therapeutic resistance. In GC, as in other malignancies, blood vessels are essential for Tumor-cell survival and dissemination, thereby facilitating metastasis to distant organs. As tumors grow, they remodel the surrounding microenvironment, generating hypoxic, acidic, nutrient-poor conditions with elevated interstitial fluid pressure. Reactive oxygen species further support tumor growth, glycolytic metabolism, and neovascularization. Highly aggressive cancer cells can also form endothelial cell-independent vascular-like networks defined as vasculogenic mimicry (VM), which may facilitate access to oxygen and nutrients. Many molecular markers and mechanisms underlying VM in GC remain insufficiently defined, while the presence of VM is associated with aggressive tumor behavior, metastatic potential, therapeutic resistance, and poor prognosis. Therefore, new therapeutic strategies are needed that complement conventional treatment and target the heterogeneous vascular compartments of GC. Nanomedicine may contribute to this goal by improving targeted drug delivery, local drug concentration, bioavailability, and controlled release while reducing systemic adverse effects.