Understanding the Clinical Use of Levosimendan and Perspectives on its Future in Oncology

Author:

Ribeiro Eduarda123ORCID,Vale Nuno124ORCID

Affiliation:

1. OncoPharma Research Group, Center for Health Technology and Services Research (CINTESIS), Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal

2. CINTESIS@RISE, Faculty of Medicine, University of Porto, Alameda Professor Hernâni Monteiro, 4200-319 Porto, Portugal

3. Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, Rua de Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal

4. Department of Community Medicine, Health Information and Decision (MEDCIDS), Faculty of Medicine, University of Porto, Rua Doutor Plácido da Costa, 4200-450 Porto, Portugal

Abstract

Drug repurposing, also known as repositioning or reprofiling, has emerged as a promising strategy to accelerate drug discovery and development. This approach involves identifying new medical indications for existing approved drugs, harnessing the extensive knowledge of their bioavailability, pharmacokinetics, safety and efficacy. Levosimendan, a calcium sensitizer initially approved for heart failure, has been repurposed for oncology due to its multifaceted pharmacodynamics, including phosphodiesterase 3 inhibition, nitric oxide production and reduction of reactive oxygen species. Studies have demonstrated that levosimendan inhibits cancer cell migration and sensitizes hypoxic cells to radiation. Moreover, it exerts organ-protective effects by activating mitochondrial potassium channels. Combining levosimendan with traditional anticancer agents such as 5-fluorouracil (5-FU) has shown a synergistic effect in bladder cancer cells, highlighting its potential as a novel therapeutic approach. This drug repurposing strategy offers a cost-effective and time-efficient solution for developing new treatments, ultimately contributing to the advancement of cancer therapeutics and improved outcomes for patients. Further investigations and clinical trials are warranted to validate the effectiveness of levosimendan in oncology and explore its potential benefits in a clinical setting.

Funder

Fundo Europeu de Desenvolvimento Regional (FEDER) funds

Publisher

MDPI AG

Subject

Molecular Biology,Biochemistry

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