‘ALL’ about metabolism: repurposing drugs for acute lymphoblastic leukaemia

T-cell acute lymphoblastic leukaemia (T-ALL) is an aggressive type of blood cancer that commonly affects children. It occurs when normal immune cells called T-cells do not develop properly. One of the first treatment options for children with T-ALL is chemotherapy. Unfortunately, a high percentage of children relapse, meaning their disease returns after treatment. This is a problem because the disease becomes resistant to treatment and more aggressive.

In this proposal, we will examine whether a group of drugs called gliflozins could be used to treat T-ALL. Gliflozins are a safe and clinically approved drug class currently used to treat type 2 diabetes because they control blood-sugar levels. Some gliflozins have additional effects and disrupt the way our cells metabolise fuels from our diet such as sugar and protein. Cancer cells adapt their metabolism – the way in which they take up and process sugar and protein – to give themselves an advantage in surviving and growing rapidly. By affecting the ways in which leukaemia cells process nutrients, we reason that certain gliflozins could work as a treatment for T-ALL. We think this could lead to better outcomes, because disrupting cancer cells’ metabolism could help to prevent them becoming resistant to treatment.

We will carry out this research in three stages – first by using cells grown in the laboratory that mimic T-ALL, secondly by testing the drugs on T-ALL samples from children, and finally seeing how the drugs work in a mouse model of T-ALL. If this research confirms our thinking, these results will inform the design of a clinical trial of gliflozins for treatment of childhood T-ALL, with the goal of reducing relapse rates and improving outcomes in aggressive forms of the disease. Since gliflozins are already prescribed safely for other purposes, these benefits could reach patients relatively rapidly.