Healthy vasculature (shown above) is characterized by orderly architecture and mature blood vessels (in green at right) that are stabilized and supported externally by smooth muscle and pericyte coats (shown in red).

Abnormal vasculature like that found in a tumor (shown above) is newly formed, highly fractured and architecturally disordered with fragile, immature blood vessels (shown in green at right) which lack external smooth muscle and pericyte support (shown in red).

The blood vessels are lined with special endothelial cells that receive external support from pericytes as well as a tubulin protein cytoskeleton, and internal support from VE-Cadherin, a protein that lines the blood vessel's inner wall.

In tumors like the one shown below, the newly formed blood vessels and the endothelial cells that line them do not have the well-organized external pericyte 'scaffolding' system to support and keep them intact.

When a vascular disrupting agent (VDA) such as ZYBRESTAT is introduced into the blood stream, it selectively targets the pathologically abnormal tumor vascular architecture, where it enters the newly formed endothelial cells, binds with the tubulin and VE-Cadherin proteins and causes the removal of the cytoskeleton and the disengagement of the endothelial cells from the blood vessel wall.

The resulting loss of support causes the detached, formerly flat endothelial cells lining the blood vessel to 'round up' blocking the flow of blood to the tumor. Like the flow of traffic, a blockage at one point in a vessel segment can shut down blood flow entirely. So, only a small number of endothelial cells within a vessel segment need to be sensitive to initiate a dramatic shutdown in blood flow to the tumor.

As seen below, collapsing the blood vessels within the tumor causes rapid, widespread cell death in the central parts of the tumor (dark area) - areas that historically have been the most resistant to conventional treatments, such as cytotoxic chemotherapy, radiation, and biologics. As a result, the tumor 'starves' from within.