Craig Jordan, PhD
Craig Jordan, PhD, University of Colorado (CU) Cancer Center member and Chief of the Hematology Division in the CU School of Medicine, was awarded a 2020 National Cancer Institute (NCI) Outstanding Investigator Award. This 7-year grant supports investigators with outstanding records of productivity in cancer research, providing more than $5.9 million in funding. Dr. Jordan and his team will use the funds to continue their research into the role of leukemia stem cells in acute myeloid leukemia (AML) and its treatment.
Targeting Stem Cells
Because existing drugs weren’t much help against leukemia stem cells, Dr. Jordan’s research team started comparing regular stem cells and leukemia stem cells to look for differences they could specifically target. They discovered that the protein BCL2 is key to the way in which leukemia stem cells create energy.
“All cells, cancer or normal, have a basic need to make energy for growth and survival,” Dr. Jordan said. “We discovered that leukemia cells use BCL2 to control energy output from mitochondria. Normal cells make energy in ways that do not require BCL2. Imagine running a car engine on ethanol vs diesel fuel. In both cases, the engine is providing power to turn the wheels, but the fuels are different. It’s not a bad analogy for leukemia vs normal stem cells. They both need the mitochondria to make energy, but the way they run the engine, so to speak, is a little different.”
Because BCL2 also prevents programmed cell death, it already was of interest to drug manufacturers. They understood that if they could create a drug that targets BCL2, it would cause cancer cells to die more quickly. However, Dr. Jordan knew that such a drug would also be helpful in treating acute myeloid leukemia, as it would cause leukemia stem cells to die due to lack of energy.
In 2014, Dr. Jordan began working with one such drug, venetoclax, which was recently approved by the U.S. Food and Drug Administration for treatment of AML in older patients unfit for intensive chemotherapy. Dr. Jordan stressed that venetoclax is no magic bullet, as most patients who take it eventually relapse.
“It kills most tumor cells and very few normal cells, so it’s tolerated much better. It puts about 70% of patients into remission, but the catch is that most of them don’t stay in remission,” he said. “But if you’re an older patient and can go into remission for a few years with a drug that doesn’t make you horribly sick, that’s a big step forward. It’s also a great starting point for building more sophisticated approaches to leukemia treatment.”