Combination of approved drugs offers new strategies for acute myeloid leukemia
The combined use of two well-known active substances can fight leukemic cells and limit their spread. This is the result of a study conducted by the Karl Landsteiner University of Health Sciences (KL Krems) and published in the journal Cancer Letters.
In experiments, the researchers discovered that an established antimalarial drug in combination with a proven anticancer drug influences the activity of a specific transcription factor and thus inhibits the expansion and spread of leukemia cells. The combination not only killed the leukemia cells, but also significantly reduced their infiltration into the bone marrow.
Acute myeloid leukemia (AML) is an aggressive form of blood cancer in which immature white blood cells proliferate in the bone marrow and interfere with normal blood cell formation. The protein STAT3 is often overactive in these cells. Attempts to inhibit its activity therapeutically have—so far—not been very successful.
The research team led by Prof. Dr. Dagmar Stoiber-Sakaguchi, head of the Division of Pharmacology at the KL Krems, has now investigated a new strategy.
STAT3 exists in two isoforms: STAT3α and STAT3β. While the α form promotes the expansion of cancer cells, the β form has an inhibitory effect. Previous work by Prof. Stoiber-Sakaguchi showed that a low ratio of STAT3β to STAT3α is associated with a poorer prognosis in AML patients.
"We therefore looked for ways to shift this ratio in a way that would provide therapeutic benefit," explains Prof. Stoiber-Sakaguchi, who is also the last author of the study. "And we succeeded."
The study focused on the combination of the antimalarial drug, which has already shown anticancer properties, with the anticancer drug selinexor.
