Mol Oncol. 2020 Sep 8. doi: 10.1002/1878-0261.12793. Online ahead of print.
More effective therapy for patients with either muscle-invasive or high-risk non-muscle invasive urothelial carcinoma of the bladder (UCB) is an unmet clinical need. For this, drug repositioning of clinically-approved drugs represents an interesting approach. By repurposing existing drugs, alternative anti-cancer therapies can be introduced in the clinic relatively fast, because the safety and dosing of these clinically-approved pharmacological agents are generally well known. CADs
dose-dependently decreased the viability of a panel of human UCB lines in vitro. CADs induced lysosomal puncta formation, a hallmark of lysosomal leakage. Intravesical instillation of the CAD penfluridol in an orthotopic mouse xenograft model of human UCB resulted in significantly reduced intravesical tumor growth and metastatic progression. Furthermore, treatment of patient-derived ex-vivo cultured human UCB tissue caused significant partial or complete anti-tumor responses in 97% of the explanted tumor tissues. In conclusion, penfluridol represents a promising treatment option for bladder cancer patients and warrants further clinical evaluation.