Antitumor Agent Penetrates Brain, Enters Clinic

Brain tumors are extraordinarily difficult to treat, in part because most drugs cannot gain access to the brain by crossing the blood-brain barrier (BBB). Waldemar Priebe and coworkers at the University of Texas M. D. Anderson Cancer Center, Houston, have designed, synthesized, and evaluated RTA744 (shown), previously called WP744, the first drug capable of crossing the BBB and inhibiting topoisomerase II, an enzyme overexpressed in brain tumors. At this month's American Association for Cancer Research meeting in Philadelphia, Priebe revealed that the drug, now licensed by Reata Pharmaceuticals, is entering Phase I clinical trials for patients with advanced brain cancer. The researchers discovered the agent by using a modular approach, building molecules from fragments that are capable of both crossing the BBB and inhibiting topo II.