Bladder cancer kills by metastasizing – usually to the lungs. A major grant from the National Cancer Institute (NCI) will help the University of Colorado Cancer Center develop new drugs aimed at stopping bladder cancer’s spread, which will kill an estimated 15,000 people in the United States this year.
“Strong preliminary work shows specific proteins that bladder cancer cells need in order to leave the bladder and attach to lung tissue. And additional work points to a number of drug candidates that block the activity of these proteins.
The current project aims to select the best drug, use medicinal chemistry to boost its effectiveness, and move the optimized drug toward a human clinical trial,” says Dan Theodorescu, MD, PhD, director of the University of Colorado Cancer Center, who will co-lead the project with David Ross, PhD, chair of the Department of Pharmaceutical Sciences at the Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of Colorado. This project is part of a recently awarded Bladder Cancer SPORE multidisciplinary NCI grant to MD Anderson.
The work is especially important in light of two current conditions: first, the extended absence of new drugs targeting bladder cancer, with the most recent advance being the addition of the drug gemcitabine, which earned FDA approval in 1997; and second, the recent explosion of technologies that allow the development of drugs that target a cancer’s specific genetic abnormalities.
“We’ve seen a paradigm shift toward targeted therapies – drugs that unlike the traditional chemotherapies selectively kill cancer cells while leaving healthy tissue unharmed. We hope to apply this paradigm to metastatic bladder cancer,” says Colin Dinney, MD, co-principal investigator of the SPORE and chair of the Department of Urology at MD Anderson.
“This project will target metastatic colonization in bladder cancer by targeting the proteins that drive these processes,” says David McConkey, PhD, co-principal investigator of the SPORE.
“As part of this project we also hope to define the biomarkers of patients likely to respond to the drugs,” Theodorescu says. Defining the population most likely to benefit from the new drugs would allow the group to select these patients for Phase I clinical trials – the project’s intended endpoint.
“We are all hopeful that three to four years from now, we’ll have a drug in clinical trials that prevents or delays the development of metastatic disease high-risk patients following treatment of the primary tumor,” Theodorescu says.
Funding provided by NCI 5P50CA091846-10