An 'energy addiction' in high-risk blood cancer stem cells could lead to new treatment strategies

Researchers at the University of Colorado Anschutz Cancer Center have uncovered a unique metabolic vulnerability in stem cells responsible for high-risk myelodysplastic syndromes (MDS), a type of aggressive blood cancer. Published in Blood Cancer Discovery, the study reveals that these cancer stem cells are highly dependent on the NAD salvage pathway, a process that maintains a molecule called NAD essential for energy production.

By targeting the enzyme NAMPT, a crucial component of this pathway, researchers were able to selectively weaken the disease-driving stem cells while leaving healthy blood-forming stem cells relatively unaffected. Dr. Eric M. Pietras, the study's co-lead author, explained that MDS stem cells exhibit an "energy addiction," relying heavily on NAD in ways that normal cells do not.

This metabolic difference creates a vulnerability that could be exploited with new drugs. The research team observed that blocking NAMPT led to a depletion of NAD, triggering an energy crisis in the cancer stem cells. This selective targeting resulted in a reduction of disease-driving cells in both patient-derived cells and animal models, while normal hematopoietic stem cells demonstrated greater adaptability.

The next step is to evaluate NAMPT-targeting drugs in clinical trials for patients with MDS and related blood cancers. The goal is to identify differences between cancer cells and healthy cells to develop more precise and effective therapies.