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Urinary Tract Tumor Organoids Reveal Eminent Differences in Drug Sensitivities When Compared to 2-Dimensional Culture Systems
Article

Data-Driven Identification of Biomarkers for In Situ Monitoring of Drug Treatment in Bladder Cancer Organoids

1
Department for Medical Technologies and Regenerative Medicine, Institute of Biomedical Engineering, University of Tuebingen, 72076 Tuebingen, Germany
2
Cluster of Excellence iFIT (EXC 2180) “Image-Guided and Functionally Instructed Tumor Therapies”, University of Tuebingen, 72076 Tuebingen, Germany
3
Institute of Applied Optics (ITO), University of Stuttgart, 70569 Stuttgart, Germany
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Mines Saint-Etienne, CNRS, UMR 6158 LIMOS, Centre CIS, Université Clermont Auvergne, 42270 Saint Jarez-en-Priest, France
5
Department of Urology, University of Tuebingen Hospital, 72076 Tuebingen, Germany
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Center of Medical Research, Department of Urology at UKT, University of Tuebingen, 72076 Tuebingen, Germany
7
NMI Natural and Medical Sciences Institute at the University of Tueingen, 72770 Reutlingen, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Giuseppe Lucarelli
Int. J. Mol. Sci. 2022, 23(13), 6956; https://doi.org/10.3390/ijms23136956
Received: 20 May 2022 / Revised: 20 June 2022 / Accepted: 21 June 2022 / Published: 23 June 2022
Three-dimensional (3D) organoid culture recapitulating patient-specific histopathological and molecular diversity offers great promise for precision medicine in cancer. In this study, we established label-free imaging procedures, including Raman microspectroscopy (RMS) and fluorescence lifetime imaging microscopy (FLIM), for in situ cellular analysis and metabolic monitoring of drug treatment efficacy. Primary tumor and urine specimens were utilized to generate bladder cancer organoids, which were further treated with various concentrations of pharmaceutical agents relevant for the treatment of bladder cancer (i.e., cisplatin, venetoclax). Direct cellular response upon drug treatment was monitored by RMS. Raman spectra of treated and untreated bladder cancer organoids were compared using multivariate data analysis to monitor the impact of drugs on subcellular structures such as nuclei and mitochondria based on shifts and intensity changes of specific molecular vibrations. The effects of different drugs on cell metabolism were assessed by the local autofluorophore environment of NADH and FAD, determined by multiexponential fitting of lifetime decays. Data-driven neural network and data validation analyses (k-means clustering) were performed to retrieve additional and non-biased biomarkers for the classification of drug-specific responsiveness. Together, FLIM and RMS allowed for non-invasive and molecular-sensitive monitoring of tumor-drug interactions, providing the potential to determine and optimize patient-specific treatment efficacy. View Full-Text
Keywords: patient-derived tumor models; personalized medicine; non-invasive molecular imaging; machine learning; drug efficacy testing patient-derived tumor models; personalized medicine; non-invasive molecular imaging; machine learning; drug efficacy testing
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MDPI and ACS Style

Becker, L.; Fischer, F.; Fleck, J.L.; Harland, N.; Herkommer, A.; Stenzl, A.; Aicher, W.K.; Schenke-Layland, K.; Marzi, J. Data-Driven Identification of Biomarkers for In Situ Monitoring of Drug Treatment in Bladder Cancer Organoids. Int. J. Mol. Sci. 2022, 23, 6956. https://doi.org/10.3390/ijms23136956

AMA Style

Becker L, Fischer F, Fleck JL, Harland N, Herkommer A, Stenzl A, Aicher WK, Schenke-Layland K, Marzi J. Data-Driven Identification of Biomarkers for In Situ Monitoring of Drug Treatment in Bladder Cancer Organoids. International Journal of Molecular Sciences. 2022; 23(13):6956. https://doi.org/10.3390/ijms23136956

Chicago/Turabian Style

Becker, Lucas, Felix Fischer, Julia L. Fleck, Niklas Harland, Alois Herkommer, Arnulf Stenzl, Wilhelm K. Aicher, Katja Schenke-Layland, and Julia Marzi. 2022. "Data-Driven Identification of Biomarkers for In Situ Monitoring of Drug Treatment in Bladder Cancer Organoids" International Journal of Molecular Sciences 23, no. 13: 6956. https://doi.org/10.3390/ijms23136956

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