Understanding the Clinical Use of Levosimendan and Perspectives on its Future in Oncology.
Eduarda RibeiroNuno ValePublished in: Biomolecules (2023)
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.
Keyphrases
- cardiac surgery
- cell migration
- drug discovery
- heart failure
- palliative care
- papillary thyroid
- induced apoptosis
- nitric oxide
- reactive oxygen species
- clinical trial
- acute kidney injury
- end stage renal disease
- healthcare
- squamous cell
- newly diagnosed
- ejection fraction
- chronic kidney disease
- oxidative stress
- prognostic factors
- emergency department
- systematic review
- signaling pathway
- spinal cord injury
- type diabetes
- cell cycle arrest
- atrial fibrillation
- peritoneal dialysis
- small molecule
- endoplasmic reticulum stress
- big data
- squamous cell carcinoma
- childhood cancer
- lymph node metastasis
- drug administration
- current status
- machine learning
- weight loss
- adipose tissue
- open label
- skeletal muscle
- electronic health record
- adverse drug
- patient reported
- case control