Pushing the accelerator and the brake at the same time is rarely a good idea. But researchers at the University of Gothenburg are using this approach to treat leukemia. A new drug forces cancer cells to keep working hard even though they have run out of energy. The first study in mice shows very promising results.
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). AML is an aggressive form of cancer affecting the blood and bone marrow, which prevents the production of red and white blood cells. The disease, which affected about one million people globally in 2015, requires immediate treatment and primarily affects adults.
Different areas of expertise
Boaz Tirosh is a biochemist and understands the processes taking place within a cell. It was he who put forward the hypothesis for this treatment. I am a computational chemist and have designed a molecule that enters the cancerous cell and alters it in the way we want."
Leif Eriksson, Professor of Physical Chemistry, University of Gothenburg
The molecule, named AcTor, inhibits a signalling protein that affects the function of the mTor protein. mTor acts as a control centre that determines when the cell should grow, build itself up or rest. The researchers' intervention ensures that mTor continues to promote full cell activity, even though energy production in the mitochondria is shut down using a standard anti-proliferative drug. The combination of treatments means that the cancer cells continue to put their foot down on the accelerator, even whilst the brake is on. This causes the cells to run amok and die from stress.
"It's a completely new method and does not affect healthy blood cells; furthermore, our studies in mice show that drug resistance is avoided, which can otherwise happen," says Leif Eriksson.
Leukemic stem cells disappeared
The study, published in Molecular Cancer, reports that AcTor had a very strong effect on leukemia in both AML cell lines and primary patient samples, as well as in animal trials, when used in combination with the inhibitor Ixazomib (IXZ). The treatment remained equally effective in TP53-mutant AML, a highly aggressive form of cancer with a poor prognosis and limited treatment options. Not only were diseased blood cells eliminated using the new method, but leukemic stem cells – which can lead to relapse – also disappeared.
"We also observed that our treatment triggered the release of a protein (ADM2), which could therefore serve as a biomarker for the treatment's response. This could guide future translational and clinical studies," says Leif Eriksson.
Validation in preclinical studies
Work is now continuing to validate the treatment in preclinical and, eventually, clinical studies. There is still a long way to go before this method is ready to treat patients with relapsed or refractory acute myeloid leukemia, who currently face limited options and a poor prognosis.
"Our study is an example of the shift towards focusing research on cancer metabolism within cells, rather than relying solely on methods that damage DNA. Drug development is very expensive, but we hope that our findings will generate sufficient interest to enable us to continue our research into a cure for this serious disease," says Leif Eriksson.
Source:
Journal reference:
Pattanayak, S. P., et al. (2026). AcTor, a novel mTOR stimulator, potentiates ixazomib for the treatment of acute myeloid leukemia. Molecular Cancer. DOI: 10.1186/s12943-026-02689-4. https://link.springer.com/article/10.1186/s12943-026-02689-4