Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1785027795712212992 |
---|---|
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. |
format | Online Article Text |
id | pubmed-10113240 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT minolimartina bladdercancerorganoidsasafunctionalsystemtomodeldifferentdiseasestagesandtherapyresponse AT cantorethomas bladdercancerorganoidsasafunctionalsystemtomodeldifferentdiseasestagesandtherapyresponse AT hanhartdaniel bladdercancerorganoidsasafunctionalsystemtomodeldifferentdiseasestagesandtherapyresponse AT kienermirjam bladdercancerorganoidsasafunctionalsystemtomodeldifferentdiseasestagesandtherapyresponse AT fedrizzitarcisio bladdercancerorganoidsasafunctionalsystemtomodeldifferentdiseasestagesandtherapyresponse AT lamannafederico bladdercancerorganoidsasafunctionalsystemtomodeldifferentdiseasestagesandtherapyresponse AT karkampounasofia bladdercancerorganoidsasafunctionalsystemtomodeldifferentdiseasestagesandtherapyresponse AT chouvardaspanagiotis bladdercancerorganoidsasafunctionalsystemtomodeldifferentdiseasestagesandtherapyresponse AT genitschvera bladdercancerorganoidsasafunctionalsystemtomodeldifferentdiseasestagesandtherapyresponse AT rodriguezcaleroantonio bladdercancerorganoidsasafunctionalsystemtomodeldifferentdiseasestagesandtherapyresponse AT comperateva bladdercancerorganoidsasafunctionalsystemtomodeldifferentdiseasestagesandtherapyresponse AT klimairena bladdercancerorganoidsasafunctionalsystemtomodeldifferentdiseasestagesandtherapyresponse AT gasperinipaola bladdercancerorganoidsasafunctionalsystemtomodeldifferentdiseasestagesandtherapyresponse AT kissbernhard bladdercancerorganoidsasafunctionalsystemtomodeldifferentdiseasestagesandtherapyresponse AT seilerroland bladdercancerorganoidsasafunctionalsystemtomodeldifferentdiseasestagesandtherapyresponse AT demichelisfrancesca bladdercancerorganoidsasafunctionalsystemtomodeldifferentdiseasestagesandtherapyresponse AT thalmanngeorgen bladdercancerorganoidsasafunctionalsystemtomodeldifferentdiseasestagesandtherapyresponse AT kruithofdejuliomarianna bladdercancerorganoidsasafunctionalsystemtomodeldifferentdiseasestagesandtherapyresponse |