Prospective pharmacotyping of urothelial carcinoma organoids for drug sensitivity prediction – feasibility and real world experience
Abstract Urothelial carcinoma (UC) of the urinary bladder has significant challenges in treatment due to its diverse genetic landscape and variable response to systemic therapy. In recent years, patient-derived organoids (PDOs) emerged as a novel tool to model primary tumors with higher resemblance...
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BMC
2024-11-01
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| Series: | Experimental Hematology & Oncology |
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| Online Access: | https://doi.org/10.1186/s40164-024-00579-3 |
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| author | Michael Karl Melzer Yanchun Ma Jessica Lindenmayer Clara Morgenstern Felix Wezel Friedemann Zengerling Cagatay Günes Nadine Therese Gaisa Alexander Kleger Christian Bolenz |
| author_facet | Michael Karl Melzer Yanchun Ma Jessica Lindenmayer Clara Morgenstern Felix Wezel Friedemann Zengerling Cagatay Günes Nadine Therese Gaisa Alexander Kleger Christian Bolenz |
| author_sort | Michael Karl Melzer |
| collection | DOAJ |
| description | Abstract Urothelial carcinoma (UC) of the urinary bladder has significant challenges in treatment due to its diverse genetic landscape and variable response to systemic therapy. In recent years, patient-derived organoids (PDOs) emerged as a novel tool to model primary tumors with higher resemblance than conventional 2D cell culture approaches. However, the potential of organoids to predict therapy response in a clinical setting remains to be evaluated. This study explores the clinical feasibility of PDOs for pharmacotyping in UC. Initially, we subjected tumor tissue specimens from 50 patients undergoing transurethral resection or radical cystectomy to organoid propagation, of whom 19 (38%) yielded PDOs suitable for drug sensitivity assessment. Notably, whole transcriptome-based analysis indicated that PDOs may show phenotypes distinct from their parental tumor tissue. Pharmacotyping within a clinically relevant timeframe [mean of 35.44 and 55 days for non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC), respectively] was achieved. Drug sensitivity analyses revealed marked differences between NMIBC and MIBC, with MIBC-derived organoids demonstrating higher chemosensitivity toward clinically relevant drugs. A case study correlating organoid response with patient treatment outcome illustrated the complexity of predicting chemotherapy efficacy, especially considering the rapid acquisition of drug resistance. We propose a workflow of prospective organoid-based pharmacotyping in UC, enabling further translational research and integration of this approach into clinical practice. |
| format | Article |
| id | doaj-art-cfc496e6e02e4966b81c02bc4a642b0d |
| institution | Kabale University |
| issn | 2162-3619 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Experimental Hematology & Oncology |
| spelling | doaj-art-cfc496e6e02e4966b81c02bc4a642b0d2024-11-17T12:13:57ZengBMCExperimental Hematology & Oncology2162-36192024-11-011311710.1186/s40164-024-00579-3Prospective pharmacotyping of urothelial carcinoma organoids for drug sensitivity prediction – feasibility and real world experienceMichael Karl Melzer0Yanchun Ma1Jessica Lindenmayer2Clara Morgenstern3Felix Wezel4Friedemann Zengerling5Cagatay Günes6Nadine Therese Gaisa7Alexander Kleger8Christian Bolenz9Department of Urology, Ulm University HospitalDepartment of Urology, Ulm University HospitalCore Facility Organoids, Ulm UniversityDepartment of Urology, Ulm University HospitalDepartment of Urology, Ulm University HospitalDepartment of Urology, Ulm University HospitalDepartment of Urology, Ulm University HospitalInstitute of Pathology, Ulm University HospitalInstitute for Molecular Oncology and Stem Cell Biology, Ulm University HospitalDepartment of Urology, Ulm University HospitalAbstract Urothelial carcinoma (UC) of the urinary bladder has significant challenges in treatment due to its diverse genetic landscape and variable response to systemic therapy. In recent years, patient-derived organoids (PDOs) emerged as a novel tool to model primary tumors with higher resemblance than conventional 2D cell culture approaches. However, the potential of organoids to predict therapy response in a clinical setting remains to be evaluated. This study explores the clinical feasibility of PDOs for pharmacotyping in UC. Initially, we subjected tumor tissue specimens from 50 patients undergoing transurethral resection or radical cystectomy to organoid propagation, of whom 19 (38%) yielded PDOs suitable for drug sensitivity assessment. Notably, whole transcriptome-based analysis indicated that PDOs may show phenotypes distinct from their parental tumor tissue. Pharmacotyping within a clinically relevant timeframe [mean of 35.44 and 55 days for non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC), respectively] was achieved. Drug sensitivity analyses revealed marked differences between NMIBC and MIBC, with MIBC-derived organoids demonstrating higher chemosensitivity toward clinically relevant drugs. A case study correlating organoid response with patient treatment outcome illustrated the complexity of predicting chemotherapy efficacy, especially considering the rapid acquisition of drug resistance. We propose a workflow of prospective organoid-based pharmacotyping in UC, enabling further translational research and integration of this approach into clinical practice.https://doi.org/10.1186/s40164-024-00579-3Patient-derived organoidsUrothelial carcinomaPharmacotyping |
| spellingShingle | Michael Karl Melzer Yanchun Ma Jessica Lindenmayer Clara Morgenstern Felix Wezel Friedemann Zengerling Cagatay Günes Nadine Therese Gaisa Alexander Kleger Christian Bolenz Prospective pharmacotyping of urothelial carcinoma organoids for drug sensitivity prediction – feasibility and real world experience Experimental Hematology & Oncology Patient-derived organoids Urothelial carcinoma Pharmacotyping |
| title | Prospective pharmacotyping of urothelial carcinoma organoids for drug sensitivity prediction – feasibility and real world experience |
| title_full | Prospective pharmacotyping of urothelial carcinoma organoids for drug sensitivity prediction – feasibility and real world experience |
| title_fullStr | Prospective pharmacotyping of urothelial carcinoma organoids for drug sensitivity prediction – feasibility and real world experience |
| title_full_unstemmed | Prospective pharmacotyping of urothelial carcinoma organoids for drug sensitivity prediction – feasibility and real world experience |
| title_short | Prospective pharmacotyping of urothelial carcinoma organoids for drug sensitivity prediction – feasibility and real world experience |
| title_sort | prospective pharmacotyping of urothelial carcinoma organoids for drug sensitivity prediction feasibility and real world experience |
| topic | Patient-derived organoids Urothelial carcinoma Pharmacotyping |
| url | https://doi.org/10.1186/s40164-024-00579-3 |
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