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

被引:10
作者
Ribeiro, Eduarda [1 ,2 ,3 ]
Vale, Nuno [1 ,2 ,4 ]
机构
[1] Ctr Hlth Technol & Serv Res CINTESIS, OncoPharma Res Grp, Rua Doutor Placido da Costa, P-4200450 Porto, Portugal
[2] Univ Porto, Fac Med, CINTESIS RISE, Alameda Prof Hernani Monteiro, P-4200319 Porto, Portugal
[3] Univ Porto, Inst Biomed Sci Abel Salazar ICBAS, Rua Jorge Viterbo Ferreira 228, P-4050313 Porto, Portugal
[4] Univ Porto, Fac Med, Dept Community Med Hlth Informat & Decis MEDCIDS, Rua Doutor Placido da Costa, P-4200450 Porto, Portugal
关键词
levosimendan; cancer; drug repurposing; drug combinations; vasodilatory mechanisms; SENSITIVE K+ CHANNEL; NONSTEROIDAL ANTIINFLAMMATORY DRUG; CELL-CYCLE ARREST; NITRIC-OXIDE; POTASSIUM CHANNELS; OXIDATIVE STRESS; PROSTATE-CANCER; HEART-FAILURE; PERMEABILITY TRANSITION; NITROSULINDAC NCX-1102;
D O I
10.3390/biom13091296
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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页数:17
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