The next stage of leukemia drug development

August 1, 2013

HSCI Principal Faculty member and Cancer Program leader Benjamin Ebert, MD, discusses the development of an animal model that allows scientists to test many possible leukemia drugs at a time, increasing the odds of finding one that eliminates cancer cells and not healthy blood cells.

Related article: "In Vivo RNAi Screening Identifies a Leukemia-Specific Dependence on Integrin Beta 3 Signaling." Cancer Cell. June 13, 2013


We know that we need new drugs to treat leukemia. We've treated leukemia with the same combinations of drugs for several decades now. It works quite well in children. We cure the majority of children with leukemia, though with considerable toxicity. But, adults, we don't do a very good job. We can get patients into remission, but their leukemia almost always recurs and is fatal when it recurs. And we can find drugs on plastic dishes, but those don't always translate very well to killing leukemia cells in an organism or in a human.

And so we wanted to develop an approach to see if we could screen lots of different targets and see which ones kill leukemia cells inside an animal. And so we developed an animal model of leukemia that develops leukemia inside a mouse and used an approach called in vivo RNA interference screening to find therapeutic targets int those leukemias. And that approach allows us to knock down or inhibit lots and lots of potential therapeutic targets at the same time, in one mouse, but if we could find all the things that kill a leukemia cell and then take those list of things and say which ones kill a normal cell, we can identify the ones that kill the bad cells and not the good ones.

And we were able to not just find one, but find several proteins that act together in a biological pathway. And if you inhibit any of those proteins you would kill the leukemia cells that we studied. And some are actually ready to move into clinical trials quite quickly. And so, that genetic screen was funded as a collaboration between HSCI and GlaxoSmithKline to identify new therapeutic targets for the treatment of cancer stem cells and that's a focus of our laboratory, and so this was a very good fit and HSCI funding and interest and advice really fostered this project.