Bladder cancer organoids as a functional system to model different disease stages and therapy response
Abstract Bladder Cancer (BLCa) inter-patient heterogeneity is the primary cause of treatment failure, suggesting that patients could benefit from a more personalized treatment approach. Patient-derived organoids (PDOs) have been successfully used as a functional model for predicting drug response in...
| Main Authors: | , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-37696-2 |
| _version_ | 1797840919958913024 |
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| author | Martina Minoli Thomas Cantore Daniel Hanhart Mirjam Kiener Tarcisio Fedrizzi Federico La Manna Sofia Karkampouna Panagiotis Chouvardas Vera Genitsch Antonio Rodriguez-Calero Eva Compérat Irena Klima Paola Gasperini Bernhard Kiss Roland Seiler Francesca Demichelis George N. Thalmann Marianna Kruithof-de Julio |
| author_facet | Martina Minoli Thomas Cantore Daniel Hanhart Mirjam Kiener Tarcisio Fedrizzi Federico La Manna Sofia Karkampouna Panagiotis Chouvardas Vera Genitsch Antonio Rodriguez-Calero Eva Compérat Irena Klima Paola Gasperini Bernhard Kiss Roland Seiler Francesca Demichelis George N. Thalmann Marianna Kruithof-de Julio |
| author_sort | Martina Minoli |
| collection | DOAJ |
| description | Abstract Bladder Cancer (BLCa) inter-patient heterogeneity is the primary cause of treatment failure, suggesting that patients could benefit from a more personalized treatment approach. Patient-derived organoids (PDOs) have been successfully used as a functional model for predicting drug response in different cancers. In our study, we establish PDO cultures from different BLCa stages and grades. PDOs preserve the histological and molecular heterogeneity of the parental tumors, including their multiclonal genetic landscapes, and consistently share key genetic alterations, mirroring tumor evolution in longitudinal sampling. Our drug screening pipeline is implemented using PDOs, testing standard-of-care and FDA-approved compounds for other tumors. Integrative analysis of drug response profiles with matched PDO genomic analysis is used to determine enrichment thresholds for candidate markers of therapy response and resistance. Finally, by assessing the clinical history of longitudinally sampled cases, we can determine whether the disease clonal evolution matched with drug response. |
| first_indexed | 2024-04-09T16:22:42Z |
| format | Article |
| id | doaj.art-506bcb5c022948ab961b87996aa3927e |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-09T16:22:42Z |
| publishDate | 2023-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-506bcb5c022948ab961b87996aa3927e2023-04-23T11:23:16ZengNature PortfolioNature Communications2041-17232023-04-0114111610.1038/s41467-023-37696-2Bladder cancer organoids as a functional system to model different disease stages and therapy responseMartina Minoli0Thomas Cantore1Daniel Hanhart2Mirjam Kiener3Tarcisio Fedrizzi4Federico La Manna5Sofia Karkampouna6Panagiotis Chouvardas7Vera Genitsch8Antonio Rodriguez-Calero9Eva Compérat10Irena Klima11Paola Gasperini12Bernhard Kiss13Roland Seiler14Francesca Demichelis15George N. Thalmann16Marianna Kruithof-de Julio17Department for BioMedical Research, Urology Research Laboratory, University of BernDepartment of Cellular, Computational and Integrative Biology, University of TrentoDepartment for BioMedical Research, Urology Research Laboratory, University of BernDepartment for BioMedical Research, Urology Research Laboratory, University of BernDepartment of Cellular, Computational and Integrative Biology, University of TrentoDepartment for BioMedical Research, Urology Research Laboratory, University of BernDepartment for BioMedical Research, Urology Research Laboratory, University of BernDepartment for BioMedical Research, Urology Research Laboratory, University of BernInstitute of Tissue Medicine and Pathology, University of BernInstitute of Tissue Medicine and Pathology, University of BernDepartment of Pathology, General Hospital, Medical University ViennaDepartment for BioMedical Research, Urology Research Laboratory, University of BernDepartment of Cellular, Computational and Integrative Biology, University of TrentoDepartment for BioMedical Research, Urology Research Laboratory, University of BernDepartment of Urology, Hospital Center BielDepartment of Cellular, Computational and Integrative Biology, University of TrentoDepartment for BioMedical Research, Urology Research Laboratory, University of BernDepartment for BioMedical Research, Urology Research Laboratory, University of BernAbstract Bladder Cancer (BLCa) inter-patient heterogeneity is the primary cause of treatment failure, suggesting that patients could benefit from a more personalized treatment approach. Patient-derived organoids (PDOs) have been successfully used as a functional model for predicting drug response in different cancers. In our study, we establish PDO cultures from different BLCa stages and grades. PDOs preserve the histological and molecular heterogeneity of the parental tumors, including their multiclonal genetic landscapes, and consistently share key genetic alterations, mirroring tumor evolution in longitudinal sampling. Our drug screening pipeline is implemented using PDOs, testing standard-of-care and FDA-approved compounds for other tumors. Integrative analysis of drug response profiles with matched PDO genomic analysis is used to determine enrichment thresholds for candidate markers of therapy response and resistance. Finally, by assessing the clinical history of longitudinally sampled cases, we can determine whether the disease clonal evolution matched with drug response.https://doi.org/10.1038/s41467-023-37696-2 |
| spellingShingle | Martina Minoli Thomas Cantore Daniel Hanhart Mirjam Kiener Tarcisio Fedrizzi Federico La Manna Sofia Karkampouna Panagiotis Chouvardas Vera Genitsch Antonio Rodriguez-Calero Eva Compérat Irena Klima Paola Gasperini Bernhard Kiss Roland Seiler Francesca Demichelis George N. Thalmann Marianna Kruithof-de Julio Bladder cancer organoids as a functional system to model different disease stages and therapy response Nature Communications |
| title | Bladder cancer organoids as a functional system to model different disease stages and therapy response |
| title_full | Bladder cancer organoids as a functional system to model different disease stages and therapy response |
| title_fullStr | Bladder cancer organoids as a functional system to model different disease stages and therapy response |
| title_full_unstemmed | Bladder cancer organoids as a functional system to model different disease stages and therapy response |
| title_short | Bladder cancer organoids as a functional system to model different disease stages and therapy response |
| title_sort | bladder cancer organoids as a functional system to model different disease stages and therapy response |
| url | https://doi.org/10.1038/s41467-023-37696-2 |
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