Repurposing amiodarone for bladder cancer treatment
Cisplatin-based neoadjuvant chemotherapy followed by radical cystectomy is the main treatment for muscle-invasive bladder cancer (MIBC). However, low survival rates highlight the necessity for new therapeutic strategies. Drug repurposing has emerged as a promising approach in cancer treatment, with various studies proposing the use of existing drugs for the treatment of bladder cancer (BC). In this context, we previously established an in silico repurposing strategy using patient -omics signatures, identifying drugs and compounds with the potential to reverse non-muscle invasive BC (NMIBC) to less aggressive subtypes. In the present study, we expanded our in silico approach to verify a list of compounds with potential anti-tumor activity against MIBC. We investigated the efficacy of the predicted candidates in a group of different BC cell lines, including NMIBC and MIBC. The most potent compound for decreasing cell viability was amiodarone, an anti-arrhythmic drug widely used in the field of cardiology. Amiodarone reduced cell proliferation and colony formation capacity, with a stronger effect on the most aggressive invasive models, validating our repurposing pipeline. The drug additionally induced cell death and inhibited the activity of mTOR and its target protein S6, suggesting that the anti-cancer effect of the drug is in part mediated by inhibition of the mTOR signaling pathway. Furthermore, the administration of amiodarone in a xenograft MIBC mouse model reduced tumor growth without inducing toxicity. Altogether, we demonstrated that amiodarone is a potential repurposed drug for BC, which might be especially effective in MIBC.