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Eur Urol. 2019 Jun 27. pii: S0302-2838(19)30501-9. doi: 10.1016/j.eururo.2019.06.016. [Epub ahead of print]

Personalized Drug Sensitivity Screening for Bladder Cancer Using Conditionally Reprogrammed Patient-derived Cells.

Author information

1
Institute of Biomedicine, University of Turku, and Department of Pathology, Turku University Hospital, Turku, Finland.
2
Department of Urology, Turku University Hospital and University of Turku, Turku, Finland.
3
Institute of Biomedicine, University of Turku, and Department of Pathology, Turku University Hospital, Turku, Finland; Department of Urology, Turku University Hospital and University of Turku, Turku, Finland.
4
Institute of Biomedicine, Research Center for Integrative Physiology and Pharmacology and Turku Center for Disease Modeling, University of Turku, Turku, Finland.
5
Misvik Biology, Turku, Finland.
6
Departments of Oncology and Pathology, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
7
Institute of Biomedicine, University of Turku, and Department of Pathology, Turku University Hospital, Turku, Finland. Electronic address: pekka.taimen@utu.fi.

Abstract

Many patients with muscle-invasive bladder cancer (BC) are either ineligible for or do not benefit from cisplatin-based chemotherapy, and there is an unmet need to estimate individuals' drug sensitivities. We investigated the suitability of conditionally reprogrammed (CR) cells for the characterization of BC properties and their feasibility for personalized drug sensitivity screening. The CR cultures were established from six BC tumors with varying histology and stage. Four cultures were successfully propagated for genomic, transcriptomic, and protein expression profiling and compared to the parental tumors. Two out of four CR cultures (urothelial carcinoma and small cell neuroendocrine carcinoma [SmCC]) corresponded well to their parental tumors and underwent drug sensitivity screening to identify novel drugs for the respective tumors. Both cultures were sensitive to standard BC chemotherapy agents (eg cisplatin and gemcitabine) and to conventional drugs such as taxanes and inhibitors of topoisomerase and proteasome. The SmCC cells were also sensitive to statins (eg, atorvastatin and pitavastatin). In summary, after confirming their representativeness and origin, we conclude that CR cells are a feasible platform for personalized drug sensitivity testing and might thus add to the approaches used to personalize BC treatment strategies. PATIENT SUMMARY: We investigated the conditional reprogramming method for generating patient-derived bladder cancer cell cultures and studied their feasibility for planning personalized treatment strategies.

KEYWORDS:

Bladder cancer; Chemotherapy; Conditional reprogramming; Drug sensitivity testing; Patient-derived cultures; Small cell carcinoma

PMID:
31256944
DOI:
10.1016/j.eururo.2019.06.016
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