Conditional Reprogramming of Patient-derived Bladder Cancer Cells for Personalized Treatment Strategies – Expert Commentary

There is a broad spectrum of bladder cancer responsiveness to treatment in the clinic. The development of practical methods to provide accurate, individualized drug sensitivity information from each patient's tumor is needed to improve outcomes.

Conditional reprogramming (CR) is a method that enables the rapid expansion of malignant and normal epithelial cells without genetic manipulation. A new study published by Kettunen et al. in European Urology assessed the use of conditionally reprogrammed cells for personalized drug sensitivity testing. The investigators developed patient-derived CR cultures from six bladder cancer samples with different histologies. Four cultures were successfully propagated for subsequent characterization. The investigators performed genomic, transcriptomic, and protein expression profiling of these primary tumors and established CR cultures. Two CR samples (urothelial carcinoma and small cell neuroendocrine carcinoma) retained the driver mutations identified in the parental tumors. 

The investigators tested the drug-sensitivity of CR patient-derived bladder cancer cells. Two cultures were sensitive to chemotherapy agents used for urothelial cancer, including cisplatin, gemcitabine, and taxanes. Interestingly, the small cell neuroendocrine carcinoma cells were sensitive to statins.  

The recent rise of two-dimensional and three-dimensional methods to establish patient-derived bladder cancer cells ex vivois a promising development. The viability of established cultures, their fidelity to the parental tumors, and the drug-testing turnaround times need to be improved to establish clinical utility. 

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine

Reference: 
Kettunen K, Boström PJ, Lamminen T, Heinosalo T, West G, Saarinen I, Kaipio K, Rantala J, Albanese C, Poutanen M, Taimen P. “Personalized Drug Sensitivity Screening for Bladder Cancer Using Conditionally Reprogrammed Patient-derived Cells.” Eur Urol. 2019 Jun 27. pii: S0302-2838(19)30501-9. doi: 10.1016/j.eururo.2019.06.016. [Epub ahead of print] PMID: 31256944





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