Tumor vasculature and extracellular space

The tumor vasculature and extracellular space are critical physiological compartments within the tumor microenvironment that support tumor progression and serve as significant barriers to effective therapy. The tumor vasculature is typically characterized by rapid, uncontrolled angiogenesis, resulting in a network of leaky, tortuous, and immature vessels that lead to high interstitial fluid pressure and regions of hypoxia (Source: Senger, D. R. & Davis, G. E., Cold Spring Harbor Perspectives in Biology, 2011). The extracellular space is filled with the extracellular matrix (ECM), a complex scaffold of proteins and polysaccharides like hyaluronan that provides structural integrity and sequesters growth factors, often forming a dense physical shield around cancer cells (Source: Henke, E. et al., Developmental Cell, 2019). Drugs targeting the vasculature, such as anti-VEGF antibodies, aim to normalize these vessels to improve drug delivery or prune them to starve the tumor of nutrients. Meanwhile, agents targeting the extracellular space, such as pegvorhyaluronidase alfa, are designed to degrade the ECM to lower physical resistance and enhance the infiltration of chemotherapy and immune cells (Source: Provenzano, P. P. et al., Cancer Cell, 2012). Together, these structural elements are major determinants of the desmoplastic response seen in aggressive cancers like pancreatic ductal adenocarcinoma.

Other names

Tumor microenvironment (structural components)Tumor stromaPerivascular spaceExtracellular matrix (ECM)

Inhibition of pro-angiogenic signaling (e.g., VEGF/VEGFR pathway) to normalize or reduce tumor blood vessel growth, and enzymatic degradation of extracellular matrix components (e.g., hyaluronan) to reduce interstitial fluid pressure and improve drug delivery.