van der Horst, Geertje; van de Merbel, Arjanneke F; Ruigrok, Eline; van der Mark, Maaike H; Ploeg, Emily; Appelman, Laura; Tvingsholm, Siri; Jäätelä, Marja; van Uhm, Janneke; Kruithof-de Julio, Marianna; Thalmann, George N.; Pelger, Rob C M; Bangma, Chris H; Boormans, Joost L; van der Pluijm, Gabri; Zwarthoff, Ellen C (2020). Cationic amphiphilic drugs as potential anticancer therapy for bladder cancer. Molecular oncology, 14(12), pp. 3121-3134. Elsevier 10.1002/1878-0261.12793
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Tha_Cationic_amphiphilic_drugs_as_potential_anticancer_therapy_for_bladder_cancer.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (9MB) | Preview |
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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie 04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology |
UniBE Contributor: |
Kruithof-de Julio, Marianna, Thalmann, George |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1878-0261 |
Publisher: |
Elsevier |
Language: |
English |
Submitter: |
Jeannine Wiemann |
Date Deposited: |
29 Dec 2020 12:42 |
Last Modified: |
05 Dec 2022 15:42 |
Publisher DOI: |
10.1002/1878-0261.12793 |
PubMed ID: |
32896947 |
Uncontrolled Keywords: |
bladder cancer cationic amphiphilic drugs ex vivo culture penfluridol preclinical in vivo model |
BORIS DOI: |
10.48350/149001 |
URI: |
https://boris.unibe.ch/id/eprint/149001 |
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