A team led by Leif Eriksson at the University of Gothenburg and Boaz Tirosh at Case Western Reserve University in Cleveland has developed a new treatment for acute myeloid leukemia (AML), an aggressive blood and bone marrow cancer that mainly strikes adults and affects around 400 people in Sweden each year.

“Boaz Tirosh is a biochemist who understands the processes at work inside a cell, and it was he who came up with the hypothesis behind this treatment. I’m a computational chemist, and I designed a molecule that enters the cancer cell and changes it the way we want,” says Leif Eriksson, professor of physical chemistry at the University of Gothenburg.

AcTor

The molecule, named AcTor, inhibits a signaling protein that affects mTOR, which acts as a control center determining when a cell grows, builds itself up, or rests. The treatment keeps mTOR pushing the cell toward full activity, even as a common inhibitor drug shuts down energy production in the mitochondria – leaving the cell’s accelerator pressed to the floor while its brakes are slammed on, until it dies from the stress.

“It’s an entirely new approach, and it doesn’t affect the blood’s healthy cells. Our studies in mice also show no resistance developing to the inhibitor drugs, which can otherwise be a problem,” says Eriksson.

Our study is an example of the shift toward targeting cancer metabolism inside the cell.

The study, published in Molecular Cancer, found that AcTor combined with the inhibitor drug ixazomib produced a strong effect on leukemia in AML cell lines, patient samples, and animal experiments – including against TP53-mutant AML, a particularly aggressive form with a poor prognosis and limited treatment options. The method eliminated not only diseased blood cells but also the leukemic stem cells that can drive relapse.

The team is now working to validate the treatment in preclinical and, eventually, clinical studies.

“Our study is an example of the shift toward targeting cancer metabolism inside the cell, rather than relying solely on DNA-damaging methods. We hope our results will draw enough interest to continue our research toward a cure for this serious disease,” says Eriksson.