Warning Sign for Cancer Drugs
Drugs That Block Tumor Blood Vessels May Harm Normal Cells
Aug. 23, 2007 - New drugs that cut off the blood supply to growing tumors may also harm normal blood vessels, mouse studies show.
The drugs are called angiogenesis inhibitors. They block a chemical signal called vascular endothelial growth factor or VEGF. Drugs that block VEGF starve tumors by keeping them from growing new blood vessels.
One such drug is Genentech's Avastin. Ironically, a new generation of more powerful drugs in the same general class -- now under development by several drug companies -- may pose even more danger, says study researcher M. Luisa Iruela-Arispe, MD, professor and vice chairwoman of molecular, cell, and developmental biology at UCLA.
"VEGF contributes to the upkeep and maintenance of the cells that line our blood vessels -- and is made by these cells themselves," Iruela-Arispe tells WebMD. "That was the first surprise from our studies. The second surprise was that we didn't know such a small amount of VEGF was so important. If we don't have it -- well, in mice, more than half die at a young age. It is like sudden death in a 35-year-old person."
Blood vessel cells make only a miniscule amount of VEGF. Most VEGF comes from other places in the body. In their studies, Iruela-Arispe and colleagues genetically engineered mice to have normal VEGF production -- except in their blood vessel cells.
The mice should have had plenty of VEGF to make up for the small amount made by the blood vessel cells, says Charles Francis, MD, director of the hemostasis and thrombosis program at the University of Rochester. Francis was not involved in the study.
"These mice should have been happy, but that was not the case," Francis tells WebMD. "A lot of these mice died as embryos or early in life. The researchers looked into this and showed that the VEGF made in the blood vessel cells is required for their survival."
VEGF Inside Cells
As it turns out, VEGF affects cells in two ways. One way is from the outside. The other way is from the inside. VEGF appears to be one of the very few chemical signals in the body that functions from inside the cell.