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

Abstract

<div><p>Many patients with <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/muscle-invasive-bladder-cancer" title="Learn more about Muscle Invasive Bladder Cancer from ScienceDirect's AI-generated Topic Pages">muscle-invasive bladder cancer</a> (BC) are either ineligible for or do not benefit from cisplatin-based chemotherapy, and there is an unmet need to estimate individuals’ <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/drug-sensitivity" title="Learn more about Drug Sensitivity from ScienceDirect's AI-generated Topic Pages">drug sensitivities</a>. 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, <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/transcriptomics" title="Learn more about Transcriptomics from ScienceDirect's AI-generated Topic Pages">transcriptomic</a>, and <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/protein-expression" title="Learn more about Protein Expression from ScienceDirect's AI-generated Topic Pages">protein expression</a> 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 <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/chemotherapy-agent" title="Learn more about Chemotherapy Agent from ScienceDirect's AI-generated Topic Pages">chemotherapy agents</a> (eg <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/cisplatin" title="Learn more about Cisplatin from ScienceDirect's AI-generated Topic Pages">cisplatin</a> and gemcitabine) and to conventional drugs such as taxanes and inhibitors of <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/topoisomerase" title="Learn more about Topoisomerase from ScienceDirect's AI-generated Topic Pages">topoisomerase</a> and <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/proteasome" title="Learn more about Proteasome from ScienceDirect's AI-generated Topic Pages">proteasome</a>. The SmCC cells were also sensitive to <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/hydroxymethylglutaryl-coenzyme-a-reductase-inhibitor" title="Learn more about Hydroxymethylglutaryl Coenzyme A Reductase Inhibitor from ScienceDirect's AI-generated Topic Pages">statins</a> (eg, <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/atorvastatin" title="Learn more about Atorvastatin from ScienceDirect's AI-generated Topic Pages">atorvastatin</a> 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.</p></div><div><h3>Patient summary</h3><p>We investigated the conditional reprogramming method for generating patient-derived <a href="https://www.sciencedirect.com/topics/medicine-and-dentistry/bladder-cancer" title="Learn more about Bladder Cancer from ScienceDirect's AI-generated Topic Pages">bladder cancer</a> cell cultures and studied their feasibility for planning personalized treatment strategies.</p></div><p></p>