Breakthrough in Leukemia Treatment
A recent study by the Karl Landsteiner University of Health Sciences (KL Krems), published in Cancer Letters, reveals that combining two well-known drugs can effectively combat leukemia cells and limit their spread. Researchers found that an antimalarial drug, when paired with a proven anticancer agent, alters the activity of a key transcription factor, ultimately inhibiting leukemia progression. This combination not only destroyed leukemia cells but also significantly reduced their infiltration into the bone marrow.
Targeting Acute Myeloid Leukemia
Acute myeloid leukemia (AML) is an aggressive blood cancer in which immature white blood cells proliferate uncontrollably, disrupting normal blood cell formation. A key protein, STAT3, is often overactive in these cancerous cells, making it a potential target for treatment. However, previous efforts to inhibit STAT3 have had limited success. Led by Prof. Dr. Dagmar Stoiber-Sakaguchi, head of the Division of Pharmacology at KL Krems, the research team explored a novel strategy to overcome this challenge.
Shifting the STAT3 Balance
STAT3 exists in two isoforms: STAT3α, which promotes cancer cell growth, and STAT3β, which has a suppressive effect. Prof. Stoiber-Sakaguchi’s earlier research linked a low STAT3β-to-STAT3α ratio with poorer AML prognosis. “We aimed to shift this ratio in a way that provides therapeutic benefit,” she explained. “And we succeeded.”
By combining atovaquone, an antimalarial drug with known anticancer properties, and selinexor, an established anticancer drug, the team successfully increased STAT3β levels. “Our experiments confirmed that this drug combination shifted the STAT3 isoform balance toward the cancer-suppressing form,” said Stefanie Weiss, first author and a doctoral student at the Medical University of Vienna. “Additionally, AML cells were destroyed, and their presence in the bone marrow was significantly reduced.”
Enhancing Adhesion to Limit Cancer Spread
The researchers also observed an increase in CD62L, a key adhesion molecule on AML cells regulated by STAT3β. “We believe that higher CD62L levels slow the spread of leukemia cells, which, as demonstrated in animal models, significantly extends survival,” Prof. Stoiber-Sakaguchi noted.
A New Therapeutic Approach
As per the press release, this study introduces a novel method for targeting STAT3 in leukemia treatment. Earlier attempts failed because they overlooked the existence of two STAT3 variants—both encoded by the same gene but differently transcribed. The KL Krems team proposes focusing on the STAT3β-to-STAT3α ratio rather than inhibiting STAT3 as a whole. By leveraging two already approved drugs, they achieved promising anticancer effects in experimental settings, opening new doors for leukemia therapy.