Chemotherapy drugs often never reach the tumors they're intended to treat, and radiation therapy is not always effective, because the blood vessels feeding the tumors are abnormal"leaky and twisty" in the words of the late Judah Folkman, MD, founder of the Vascular Biology program at Children's Hospital Boston. Now, Vascular Biology researchers have discovered an explanation for these abnormalities that could, down the road, improve chemotherapy drug delivery. Their findings were published in the August 12 issue of the Proceedings of the National Academy of Sciences.
A tumor's capillariessmall blood vessels that directly deliver oxygen and nutrients to cancer cellsare irregularly shaped, being excessively thin in some areas and forming thick, snarly clumps in others. These malformations create a turbulent, uneven blood flow, so that too much blood goes to one region of the tumor, and too little to another. In addition, the capillary endothelial cells lining the inner surface of tumor capillaries, normally a smooth, tightly-packed sheet, have gaps between them, causing vessel leakiness.
"These abnormal features of tumor vessels impair delivery of circulating chemotherapeutic drugs to the actual tumor site" says Kaustabh Ghosh, PhD, first author on the paper, and a postdoctoral fellow in the laboratory of Donald Ingber, MD, PhD, the paper's senior author and interim co-director of the Vascular Biology program.
The idea of a therapy aimed at normalizing a tumor's blood vessels, to ensure that chemotherapeutic agents reach the tumor, has already been explored, but these attempts have only targeted soluble factors, particularly vascular endothelial growth factor (VEGF). Tumors secrete VEGF in abundance; it not only promotes blood vessel growth (angiogenesis), but makes them leaky. While blocking VEGF action helps reduce leakiness and improves vessel function, the effects have been transient, Ghosh says.