Scientists from the University of Gothenburg report a breakthrough in combating acute myeloid leukemia (AML), a fast-growing blood and bone marrow cancer. Under the direction of Leif Eriksson and Boaz Tirosh, researchers engineered a compound that exhausts AML cells by forcing them to sustain high activity despite depleted energy reserves, ultimately leading to cellular “burnout” and death.
The disease, which affected about one million people globally in 2015, requires immediate treatment and primarily affects adults. AML prevents the production of red and white blood cells, and current treatment options are limited.
According to Leif Eriksson, Professor of Physical Chemistry at the University of Gothenburg, the new 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.
Treatment Method
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. Leif Eriksson notes that the method is completely new and does not affect healthy blood cells. Furthermore, studies in mice show that drug resistance is avoided, which can otherwise happen.
Research Team and AcTor’s Role
Boaz Tirosh, a biochemist, proposed the hypothesis underlying the treatment. Leif Eriksson, a computational chemist, designed the molecule that enters cancer cells and modifies them as intended.
The paper lists Pattanayak SP, Darawshi O, Hajihassani O, Winter JM, Weiler N, Ott M, Rothweiler F and Cinatl J Jr as co-authors. Additional authors include Michaelis M, Lindner DJ, Green TD, Krassovskaia P, Aruleba RT, Fisher-Wellman KH, Mears JA, Wald D, Eriksson LA and Tirosh B. AcTor is a novel mTOR stimulator that potentiates ixazomib for treating acute myeloid leukemia.
Study Results
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. The researchers also observed that their treatment triggered the release of a protein (ADM2), which could serve as a biomarker for the treatment’s response.
Work is now continuing to validate the treatment in preclinical and, eventually, clinical studies. While there is still a long way to go before this method is ready to treat patients with relapsed or refractory acute myeloid leukemia, the researchers hope that their findings will generate sufficient interest to enable them to continue their research into a cure for this serious disease.
Leave a Reply