Cationic amphiphilic drugs as potential anticancer therapy for bladder cancer
Molecular Oncology , Volume 14 - Issue 12 p. 3121- 3134
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.
|bladder cancer, cationic amphiphilic drugs, ex vivo culture, penfluridol, preclinical in vivo model|
|Organisation||Department of Pediatric Surgery|
van der Horst, G., van de Merbel, A.F., Ruigrok, E., van der Mark, M.H., van der Ploeg, E., Appelman, L., … Zwarthoff, E.C. (2020). Cationic amphiphilic drugs as potential anticancer therapy for bladder cancer. Molecular Oncology, 14(12), 3121–3134. doi:10.1002/1878-0261.12793