Tumor and endothelial cell microvasculature

The tumor and endothelial cell microvasculature refers to the specialized and often aberrant network of blood vessels that develops within a tumor to support its metabolic demands. Unlike healthy vasculature, tumor microvasculature is characterized by structural abnormalities, such as irregular branching, leakiness, and a lack of distinct basement membranes, primarily driven by an overproduction of pro-angiogenic factors like Vascular Endothelial Growth Factor (VEGF) (NCI, 2023). This system serves as a critical therapeutic target in oncology, where interventions aim to either inhibit the growth of new vessels (anti-angiogenesis) or selectively destroy the existing tumor blood supply (vascular disrupting agents) (Nature Reviews Cancer, 2011). Anti-angiogenic drugs, such as bevacizumab, work by neutralizing ligands like VEGF or blocking their receptors (VEGFR), thereby starving the tumor of oxygen and nutrients. Conversely, vascular disrupting agents (VDAs) like fosbretabulin target the tubulin cytoskeleton of established tumor endothelial cells, leading to rapid vessel collapse and extensive tumor necrosis. Targeting the microvasculature can also 'normalize' the remaining vessels, reducing interstitial fluid pressure and improving the delivery of co-administered cytotoxic drugs (Frontiers in Oncology, 2023). However, affecting this target is associated with significant safety concerns, including hypertension, proteinuria, and impaired wound healing, due to the role of similar pathways in normal physiological processes. Monitoring biomarkers such as circulating endothelial cells and imaging parameters like Ktrans can help assess the efficacy of these therapies in clinical settings.

Other names

Tumor vasculatureTumor microvasculatureTumor-associated endothelial cellsTumor blood vesselsTumor-associated vasculature

Inhibition of pro-angiogenic signaling (e.g., VEGF/VEGFR, Ang/Tie2) to prevent new vessel formation, or direct disruption of the tubulin cytoskeleton in endothelial cells to collapse existing tumor vessels.