Inside a laboratory in Aurora, Colorado, scientists have discovered something that could change how we treat a deadly blood cancer. Researchers at the University of Colorado Anschutz Cancer Center found that the most dangerous cancer cells in high-risk MDS — a group of blood cancers where the bone marrow fails to make healthy blood cells — have a surprising weakness. These harmful cells are heavily dependent on NAD, a tiny molecule that acts like fuel for cells.
Eric M. Pietras, an associate professor in the Division of Hematology at the University of Colorado, co-led the study. He explained it this way: the cancer stem cells use energy in completely different ways than healthy stem cells do. They rely on a specific set of proteins and processes that creates an opening — a vulnerability — that doctors might one day target with new drugs.
MDS, which stands for myelodysplastic syndromes, affects mostly older adults. Each year, between 10,000 and 20,000 people in the United States are diagnosed with this cancer. Patients often develop severe anemia, get sick from infections more easily, and may need regular blood transfusions. In its most dangerous form, MDS can progress to acute myeloid leukemia, or AML, a fast-moving blood cancer that has been difficult to treat.
The research team, whose work was published in the journal Blood Cancer Discovery, focused on understanding what makes cancer stem cells different from healthy ones. They found that high-risk MDS stem cells depend heavily on something called the NAD salvage pathway — a recycling system that keeps NAD levels stable inside cells. A key enzyme in this pathway, called NAMPT, stood out as a promising target for treatment.
Pietras described the phenomenon as an "energy addiction." Unlike healthy blood-forming stem cells, which can switch to alternative energy sources when needed, MDS stem cells get stuck when their preferred pathway is blocked. They run out of fuel and weaken. The researchers tested this by blocking NAMPT in both patient-derived MDS cells and animal models. The results showed that targeting this energy pathway reduced the number of disease-driving stem cells, while healthy stem cells were better able to adapt and survive.
"These cells had developed a much greater need for this resource," Pietras said. "They appear to use NAD at a much higher rate than normal cells, which creates a vulnerability that we can exploit with new types of drugs."
The next step is to evaluate NAMPT-targeting drugs in clinical studies for patients with MDS and related blood cancers. Sweta B. Patel, Ph.D., led the laboratory work for the project. She and her colleagues hope this finding will eventually lead to more precise treatments that hit cancer cells hard while leaving healthy cells largely untouched.
"Our goal is to identify approaches that make these complex diseases more treatable by finding the differences between cancer cells and normal cells," Pietras said. "If we can understand those differences, we can begin to develop therapies that are more precise and more effective for patients."
For the roughly 10,000 to 20,000 Americans diagnosed with MDS every year, this discovery offers a new avenue of hope — and a reminder that science is steadily uncovering the weak spots in even the most aggressive cancers.