Repurposing Amiodarone for Bladder Cancer Treatment.

Area of Science:

• Oncology
• Pharmacology
• Drug Repurposing

Background:

• Muscle-invasive bladder cancer (MIBC) treatment relies on chemotherapy and surgery, but survival rates necessitate novel therapeutic strategies.
• Drug repurposing offers a viable approach to identify new bladder cancer treatments from existing medications.
• Previous in silico work identified compounds for nonmuscle-invasive bladder cancer (NMIBC); this study extends the approach to MIBC.

Purpose of the Study:

• To identify and validate repurposed drugs with potential antitumor activity against muscle-invasive bladder cancer (MIBC).
• To investigate the efficacy of amiodarone, an antiarrhythmic drug, in preclinical bladder cancer models.

Main Methods:

• An in silico drug repurposing strategy was employed to predict compounds effective against MIBC.
• The efficacy of predicted candidates, including amiodarone, was evaluated in vitro using bladder cancer cell lines (NMIBC and MIBC).
• In vivo efficacy and toxicity were assessed using a xenograft MIBC mouse model.

Main Results:

• Amiodarone demonstrated the most potent inhibition of cell viability, proliferation, and colony formation across bladder cancer cell lines, particularly in aggressive MIBC models.
• Amiodarone induced cell death and inhibited the mTOR signaling pathway.
• In vivo, amiodarone significantly reduced tumor growth in a xenograft MIBC mouse model without observable toxicity.

Conclusions:

• Amiodarone is a potential repurposed drug for bladder cancer treatment.
• The findings suggest amiodarone's anticancer effects are partly mediated by mTOR pathway inhibition.
• Amiodarone may be particularly effective for muscle-invasive bladder cancer (MIBC).