Cationic amphiphilic drugs as potential anticancer therapy for bladder cancer. Issue 12 (16th October 2020) - van der Horst, Geertje
Abstract : 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 anticancer therapies can be introduced in the clinic relatively fast, because the safety and dosing of these clinically approved pharmacological agents are generally well known. Cationic amphiphilic drugs (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 antitumor 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. Abstract : Repurposing FDA‐approved, antipsychotic cationic amphiphilic drugs like penfluridol dose‐dependently decreased viability of human bladder cancer cells, significantly reduced tumor progression and metastasis in an orthotopic human bladder cancer xenograft model, and induced significant antitumor responses in patient‐derived, ex vivo cultured bladder cancer tissue. Clinically approved penfluridol is a promising antineoplastic agent for bladder cancer patients for which effective therapy is currently lacking.