Uridine is a Targetable Metabolic Dependency in Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children and remains a leading cause of cancer-related death. Most of these deaths occur due to relapse. The goal of our research is to identify cells that can cause relapse and understand what is distinct about cells capable of causing relapse to develop new targets for treatment. We have identified that cells associated with relapse use glucose (sugar) in a distinct way and without glucose, these cells cannot survive. Instead of using glucose for energy, ALL cells associated with relapse use glucose to produce uridine, a key metabolite in many important cellular pathways. We believe this may be of particular importance in certain genetic subsets of ALL, several of with are at higher risk of relapse and without specific drug targets. We can target uridine production using an inhibitor of this pathway. Treating ALL cells with this inhibitor efficiently kills ALL cells. Thus, we believe that developing treatments to target uridine production may improve relapse outcomes for patients with ALL.
Project Goals
There are 3 main goals for this project:
1. To determine what genetic subtypes of ALL are dependent on glucose to produce uridine.
2. To determine the effectiveness of a drug targeting uridine production in ALL pre-clinical models.
3. To determine why ALL cells require uridine and determine if uridine leads to chemotherapy resistance.
Together, we believe this work will help us advance a novel therapy childhood cancer towards a clinical trial and bring us closer to our ultimate goal, preventing relapse for children with ALL.
