Tumor vasculature and tumor interstitium

The tumor vasculature and tumor interstitium are physiological compartments within the tumor microenvironment (TME) that play a decisive role in tumor growth, metastasis, and therapeutic resistance. Tumor blood vessels are structurally and functionally abnormal, being characterized by excessive branching, leakiness, and a lack of basement membrane integrity, which results in heterogeneous blood flow and hypoxia (Jain, R. K., Science, 2005). The tumor interstitium consists of a collagen-rich extracellular matrix and a fluid phase with high interstitial fluid pressure (IFP), which acts as a physiological barrier to the delivery of both small-molecule and macromolecular drugs (Heldin et al., Nature Reviews Cancer, 2004). Therapeutic interventions targeting these areas include anti-angiogenic agents like bevacizumab, which inhibits VEGF to normalize the vasculature, and vascular disrupting agents (VDAs) like fosbretabulin, which cause rapid collapse of the tumor's existing blood supply (Tozer et al., Nature Reviews Cancer, 2005). Additionally, the high permeability of tumor vessels is exploited by nanomedicines via the Enhanced Permeability and Retention (EPR) effect to facilitate passive targeting of the tumor interstitium (Maeda et al., Journal of Controlled Release, 2000).

Other names

Tumor microenvironmentTumor stromaTumor blood vesselsExtracellular matrixTumor-associated vasculature

Inhibition of angiogenesis via VEGF/VEGFR blockade, vascular disruption through tubulin depolymerization, and normalization of tumor vasculature to reduce interstitial fluid pressure and improve drug delivery.