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Bladder cancer organoids as a functional system to model different disease stages and therapy response

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 differen...

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Autores principales: Minoli, Martina, Cantore, Thomas, Hanhart, Daniel, Kiener, Mirjam, Fedrizzi, Tarcisio, La Manna, Federico, Karkampouna, Sofia, Chouvardas, Panagiotis, Genitsch, Vera, Rodriguez-Calero, Antonio, Compérat, Eva, Klima, Irena, Gasperini, Paola, Kiss, Bernhard, Seiler, Roland, Demichelis, Francesca, Thalmann, George N., Kruithof-de Julio, Marianna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113240/
https://www.ncbi.nlm.nih.gov/pubmed/37072390
http://dx.doi.org/10.1038/s41467-023-37696-2
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author Minoli, Martina
Cantore, Thomas
Hanhart, Daniel
Kiener, Mirjam
Fedrizzi, Tarcisio
La Manna, Federico
Karkampouna, Sofia
Chouvardas, Panagiotis
Genitsch, Vera
Rodriguez-Calero, Antonio
Compérat, Eva
Klima, Irena
Gasperini, Paola
Kiss, Bernhard
Seiler, Roland
Demichelis, Francesca
Thalmann, George N.
Kruithof-de Julio, Marianna
author_facet Minoli, Martina
Cantore, Thomas
Hanhart, Daniel
Kiener, Mirjam
Fedrizzi, Tarcisio
La Manna, Federico
Karkampouna, Sofia
Chouvardas, Panagiotis
Genitsch, Vera
Rodriguez-Calero, Antonio
Compérat, Eva
Klima, Irena
Gasperini, Paola
Kiss, Bernhard
Seiler, Roland
Demichelis, Francesca
Thalmann, George N.
Kruithof-de Julio, Marianna
author_sort Minoli, Martina
collection PubMed
description 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.
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spelling pubmed-101132402023-04-20 Bladder cancer organoids as a functional system to model different disease stages and therapy response Minoli, Martina Cantore, Thomas Hanhart, Daniel Kiener, Mirjam Fedrizzi, Tarcisio La Manna, Federico Karkampouna, Sofia Chouvardas, Panagiotis Genitsch, Vera Rodriguez-Calero, Antonio Compérat, Eva Klima, Irena Gasperini, Paola Kiss, Bernhard Seiler, Roland Demichelis, Francesca Thalmann, George N. Kruithof-de Julio, Marianna Nat Commun Article 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. Nature Publishing Group UK 2023-04-18 /pmc/articles/PMC10113240/ /pubmed/37072390 http://dx.doi.org/10.1038/s41467-023-37696-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Minoli, Martina
Cantore, Thomas
Hanhart, Daniel
Kiener, Mirjam
Fedrizzi, Tarcisio
La Manna, Federico
Karkampouna, Sofia
Chouvardas, Panagiotis
Genitsch, Vera
Rodriguez-Calero, Antonio
Compérat, Eva
Klima, Irena
Gasperini, Paola
Kiss, Bernhard
Seiler, Roland
Demichelis, Francesca
Thalmann, George N.
Kruithof-de Julio, Marianna
Bladder cancer organoids as a functional system to model different disease stages and therapy response
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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10113240/
https://www.ncbi.nlm.nih.gov/pubmed/37072390
http://dx.doi.org/10.1038/s41467-023-37696-2
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