Personalized Drug Sensitivity Screening for Bladder Cancer Using Conditionally Reprogrammed Patient-derived Cells
Gun West; Katja Kaipio; Kimmo Kettunen; Tarja Lamminen; Chris Albanese; Peter J. Boström; Juha Rantala; Matti Poutanen; Taija Heinosalo; Irena Saarinen; Pekka Taimen
https://urn.fi/URN:NBN:fi-fe2021042823973
Tiivistelmä
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.
Kokoelmat
- Rinnakkaistallenteet [19207]