A1 Refereed original research article in a scientific journal

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




AuthorsKimmo Kettunen, Peter J. Boström, Tarja Lamminen, Taija Heinosalo, Gun West , Irena Saarinen, Katja Kaipio, Juha Rantala, Chris Albanese, Matti Poutanen, Pekka Taimen

PublisherElsevier B.V.

Publication year2019

JournalEuropean Urology

Journal name in sourceEuropean Urology

Volume76

Issue4

First page 430

Last page434

Number of pages5

ISSN0302-2838

eISSN1873-7560

DOIhttps://doi.org/10.1016/j.eururo.2019.06.016

Web address https://www.sciencedirect.com/science/article/pii/S0302283819305019

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/detail/Publication/41458719


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.


Downloadable publication

This is an electronic reprint of the original article.
This reprint may differ from the original in pagination and typographic detail. Please cite the original version.





Last updated on 2024-26-11 at 21:28