Combination of Approved Drugs Offers New Strategies for Acute Myeloid Leukemia
Antimalarial drug together with anticancer drug is efficient against leukemia. KL Krems study shows synergistic effect.
(firmenpresse) - Krems (Austria), March 5, 2025: 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 recently 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.
Tiny Shifts. Big Impact.
STAT3 exists in two isoforms: STAT3alpha and STAT3beta. While the alpha form promotes the expansion of cancer cells, the beta form has an inhibitory effect. Previous work by Prof. Stoiber-Sakaguchi showed that a low ratio of STAT3beta to STAT3alpha 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 atovaquone, which has already shown anticancer properties, with the anticancer drug selinexor. "We were able to demonstrate that this combination changes the STAT3 isoform ratio in favor of the beta-form under experimental conditions," explains Stefanie Weiss, first author of the study and a doctoral student at the Medical University of Vienna. "In addition, the AML cells were killed and their presence in the bone marrow was significantly reduced”.
More Adhesion. Less Spread.
The team also observed an increased production of the protein CD62L. CD62L is an adhesion molecule on the surface of AML cells whose expression is up-regulated by STAT3beta. "We suspect that increased expression of the adhesion molecule CD62L leads to a delay in the spread of leukemia cells and thus, as shown in animal models, significantly prolongs survival," explains Prof. Stoiber-Sakaguchi.
In summary, this work opens a new avenue for utilizing cancer therapeutics targeting the STAT3 protein. Previous approaches to inhibit STAT3 did not achieve the desired effect because they did not consider that STAT3 exists in two variants – encoded by the same gene but transcribed differently. The KL Krems team now proposes to focus on the ratio of STAT3beta to STAT3alpha and to specifically influence it. At least experimentally, they achieved an anti-cancer effect by combining two already approved and established substances.
Original publication: Atovaquone and selinexor as a novel combination treatment option in acute myeloid leukemia. S. Weiss, B. Zdársky, A. Witalisz-Siepracka, S. Edtmayer, A. Holzer, K. Heindl, E. Casanova, K. Podar & D. Stoiber. Cancer Letters 613 (2025) doi 10.1016/j.canlet.2025.21750. https://kris.kl.ac.at/de/publications/atovaquone-and-selinexor-as-a-novel-combination-treatment-option-
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Karl Landsteiner University of Health Sciences (03/2025)
The Karl Landsteiner University of Health Sciences (KL Krems) is an educational and research institution on the Campus Krems and recognised throughout Europe. KL Krems offers modern, demand-oriented education and continuing education in medicine and psychology as well as a PhD programme in Mental Health and Neuroscience. The flexible educational programme is tailored to the needs of students, the requirements of the labour market and the challenges of science. The three university hospitals in Krems, St. Pölten and Tulln and the MedAustron Ion Therapy and Research Centre in Wiener Neustadt guarantee clinical teaching and research of the highest quality. In its research, KL Krems focuses on interdisciplinary fields with high relevance to health policy - including biomechanics, molecular oncology, mental health and neuroscience as well as the topic of water quality and the associated health aspects. KL Krems was founded in 2013 and accredited by the Austrian Agency for Quality Assurance and Accreditation (AQ Austria).
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Datum: 05.03.2025 - 12:24 Uhr
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