Averting danger from within

A factor that promotes blood vessel growth keeps two types of brain cells alive, say Maharaj et al. (page 491). Their findings might explain why anticancer drugs that block this factor cause neurological side effects. The drug target in question—vascular endothelial growth factor (VEGF)— binds to receptors on blood vessel endothelial cells. A localized increase in VEGF, which is produced by underlying epithelial cells and other neighboring cells, promotes vessel growth in developing organs and injured tissues. Lower levels of VEGF might also be necessary for the survival of endothelial cells, which become apoptotic when cultured in the absence of VEGF. VEGF-blocking drugs that limit tumor growth by inhibiting the tumors’ blood supply can cause seizures and brain swelling in some cancer patients. To find out whether these symptoms stem from the destruction of brain blood vessels, Maharaj et al. examined the brains of mice that had been engineered to express high levels of proteins that block VEGF and TGFβ—a cytokine that stimulates VEGF production. Besides damage to brain endothelia, the mice developed brain lesions due to a breakdown of the barrier that prevents cerebral spinal fluid from seeping into the brain. The specialized type of epithelial cells that make up this barrier expressed VEGF receptors and became apoptotic when VEGF was systemically blocked. Why brain complications only occur in a subset of cancer patients on anti-VEGF therapy is unknown. Averting danger from within