Researchers have unveiled a new approach to treat acute myeloid leukemia that pushes cancer cells to keep working even when their energy supplies are cut off.
Targeting leukemia metabolism
The disease, an aggressive blood and bone-marrow cancer, struck roughly one million people worldwide in 2015 and mainly affects adults.
A collaborative team from University of Gothenburg and Case Western Reserve University led the work, with Leif Eriksson handling computational chemistry and Boaz Tirosh contributing biochemistry expertise.
“Boaz Tirosh is a biochemist and understands the processes taking place within a cell. He 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,” Eriksson said.
The designed molecule, called AcTor, blocks a signaling protein that normally regulates the mTOR pathway, a central hub that tells cells when to grow or rest.
When combined with a standard anti-proliferative drug that disables mitochondrial energy production, the compound forces mTOR to stay active. The cancer cells thus keep pressing the accelerator while the brake is applied, leading to lethal stress.
Eriksson noted that the method spares healthy blood cells and, in mouse experiments, appears to prevent the emergence of drug-resistant clones. The studies used immunocompromised mice engrafted with human leukemia cells, allowing observation of tumor trends in a living organism.
Promising results in pre-clinical tests
The findings, published in Molecular Cancer, show that it dramatically reduced leukemia burden in both cell-line models and primary patient samples when paired with the proteasome inhibitor Ixazomib.
Effectiveness persisted in the TP53-mutant form of the disease, a subtype known for poor outcomes and limited treatment options. Importantly, the therapy also eliminated leukemic stem cells that often drive relapse.
The team also detected increased release of the protein ADM2 after treatment, proposing it as a possible biomarker to monitor therapeutic response. Because ADM2 circulates in the bloodstream, measuring its levels could provide clinicians with a minimally invasive way to gauge how well the treatment is working.
Path toward clinical use
Further work will focus on preclinical validation before moving into human trials, targeting patients with relapsed or refractory disease who currently have few options.
“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,” Eriksson said.
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