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While multi-drug combinations and continuous treatment have become standard for multiple myeloma, the disease remains incurable. Repurposing drugs that are currently used for other indications could provide a novel approach to improve the therapeutic efficacy of standard multiple myeloma treatments. Here, we assessed the anti-tumor effects of cardiac drugs called β-blockers as a single agent and in combination with commonly used anti-myeloma therapies. Expression of the β 2-adrenergic receptor correlated with poor survival outcomes in patients with multiple myeloma. Targeting the β 2-adrenergic receptor (β 2AR) using either selective or non-selective β-blockers reduced multiple myeloma cell viability, and induced apoptosis and autophagy. Blockade of the β 2AR modulated cancer cell metabolism by reducing the mitochondrial respiration as well as the glycolytic activity. These effects were not observed by blockade of β 1-adrenergic receptors. Combining β 2AR blockade with the chemotherapy drug melphalan or the proteasome inhibitor bortezomib significantly increased apoptosis in multiple myeloma cells. These data identify the therapeutic potential of β 2AR-blockers as a complementary or additive approach in multiple myeloma treatment and support the future clinical evaluation of non-selective β-blockers in a randomized controlled trial.
Bibliografische notaFunding Information:
We thank Charlotte Van De Walle and Carine Seynaeve for their laboratory assistance. This study was supported by the Vrije Universiteit Brussel (VUB) spearhead research programs. KDV is a postdoctoral fellow of FWO Vlaanderen (12I0921N). IO and NV are predoctoral fellows of FWO Vlaanderen (1159622N, 1S66121N). EKS is supported by NHMRC 1147498, 2002772; National Breast Cancer Foundation IIRS-20-025; and the Cancer Council Victoria Grant-in-Aid Scheme. AM is supported by FWO (I001420N).
© 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Copyright 2022 Elsevier B.V., All rights reserved.
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