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A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds

The inter- and intra-tumor heterogeneity of breast cancer needs to be adequately captured in pre-clinical models. We have created a large collection of breast cancer patient-derived tumor xenografts (PDTXs), in which the morphological and molecular characteristics of the originating tumor are preser...

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Autores principales: Bruna, Alejandra, Rueda, Oscar M., Greenwood, Wendy, Batra, Ankita Sati, Callari, Maurizio, Batra, Rajbir Nath, Pogrebniak, Katherine, Sandoval, Jose, Cassidy, John W., Tufegdzic-Vidakovic, Ana, Sammut, Stephen-John, Jones, Linda, Provenzano, Elena, Baird, Richard, Eirew, Peter, Hadfield, James, Eldridge, Matthew, McLaren-Douglas, Anne, Barthorpe, Andrew, Lightfoot, Howard, O’Connor, Mark J., Gray, Joe, Cortes, Javier, Baselga, Jose, Marangoni, Elisabetta, Welm, Alana L., Aparicio, Samuel, Serra, Violeta, Garnett, Mathew J., Caldas, Carlos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037319/
https://www.ncbi.nlm.nih.gov/pubmed/27641504
http://dx.doi.org/10.1016/j.cell.2016.08.041
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author Bruna, Alejandra
Rueda, Oscar M.
Greenwood, Wendy
Batra, Ankita Sati
Callari, Maurizio
Batra, Rajbir Nath
Pogrebniak, Katherine
Sandoval, Jose
Cassidy, John W.
Tufegdzic-Vidakovic, Ana
Sammut, Stephen-John
Jones, Linda
Provenzano, Elena
Baird, Richard
Eirew, Peter
Hadfield, James
Eldridge, Matthew
McLaren-Douglas, Anne
Barthorpe, Andrew
Lightfoot, Howard
O’Connor, Mark J.
Gray, Joe
Cortes, Javier
Baselga, Jose
Marangoni, Elisabetta
Welm, Alana L.
Aparicio, Samuel
Serra, Violeta
Garnett, Mathew J.
Caldas, Carlos
author_facet Bruna, Alejandra
Rueda, Oscar M.
Greenwood, Wendy
Batra, Ankita Sati
Callari, Maurizio
Batra, Rajbir Nath
Pogrebniak, Katherine
Sandoval, Jose
Cassidy, John W.
Tufegdzic-Vidakovic, Ana
Sammut, Stephen-John
Jones, Linda
Provenzano, Elena
Baird, Richard
Eirew, Peter
Hadfield, James
Eldridge, Matthew
McLaren-Douglas, Anne
Barthorpe, Andrew
Lightfoot, Howard
O’Connor, Mark J.
Gray, Joe
Cortes, Javier
Baselga, Jose
Marangoni, Elisabetta
Welm, Alana L.
Aparicio, Samuel
Serra, Violeta
Garnett, Mathew J.
Caldas, Carlos
author_sort Bruna, Alejandra
collection PubMed
description The inter- and intra-tumor heterogeneity of breast cancer needs to be adequately captured in pre-clinical models. We have created a large collection of breast cancer patient-derived tumor xenografts (PDTXs), in which the morphological and molecular characteristics of the originating tumor are preserved through passaging in the mouse. An integrated platform combining in vivo maintenance of these PDTXs along with short-term cultures of PDTX-derived tumor cells (PDTCs) was optimized. Remarkably, the intra-tumor genomic clonal architecture present in the originating breast cancers was mostly preserved upon serial passaging in xenografts and in short-term cultured PDTCs. We assessed drug responses in PDTCs on a high-throughput platform and validated several ex vivo responses in vivo. The biobank represents a powerful resource for pre-clinical breast cancer pharmacogenomic studies (http://caldaslab.cruk.cam.ac.uk/bcape), including identification of biomarkers of response or resistance.
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spelling pubmed-50373192016-09-30 A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds Bruna, Alejandra Rueda, Oscar M. Greenwood, Wendy Batra, Ankita Sati Callari, Maurizio Batra, Rajbir Nath Pogrebniak, Katherine Sandoval, Jose Cassidy, John W. Tufegdzic-Vidakovic, Ana Sammut, Stephen-John Jones, Linda Provenzano, Elena Baird, Richard Eirew, Peter Hadfield, James Eldridge, Matthew McLaren-Douglas, Anne Barthorpe, Andrew Lightfoot, Howard O’Connor, Mark J. Gray, Joe Cortes, Javier Baselga, Jose Marangoni, Elisabetta Welm, Alana L. Aparicio, Samuel Serra, Violeta Garnett, Mathew J. Caldas, Carlos Cell Resource The inter- and intra-tumor heterogeneity of breast cancer needs to be adequately captured in pre-clinical models. We have created a large collection of breast cancer patient-derived tumor xenografts (PDTXs), in which the morphological and molecular characteristics of the originating tumor are preserved through passaging in the mouse. An integrated platform combining in vivo maintenance of these PDTXs along with short-term cultures of PDTX-derived tumor cells (PDTCs) was optimized. Remarkably, the intra-tumor genomic clonal architecture present in the originating breast cancers was mostly preserved upon serial passaging in xenografts and in short-term cultured PDTCs. We assessed drug responses in PDTCs on a high-throughput platform and validated several ex vivo responses in vivo. The biobank represents a powerful resource for pre-clinical breast cancer pharmacogenomic studies (http://caldaslab.cruk.cam.ac.uk/bcape), including identification of biomarkers of response or resistance. Cell Press 2016-09-22 /pmc/articles/PMC5037319/ /pubmed/27641504 http://dx.doi.org/10.1016/j.cell.2016.08.041 Text en © 2016 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Resource
Bruna, Alejandra
Rueda, Oscar M.
Greenwood, Wendy
Batra, Ankita Sati
Callari, Maurizio
Batra, Rajbir Nath
Pogrebniak, Katherine
Sandoval, Jose
Cassidy, John W.
Tufegdzic-Vidakovic, Ana
Sammut, Stephen-John
Jones, Linda
Provenzano, Elena
Baird, Richard
Eirew, Peter
Hadfield, James
Eldridge, Matthew
McLaren-Douglas, Anne
Barthorpe, Andrew
Lightfoot, Howard
O’Connor, Mark J.
Gray, Joe
Cortes, Javier
Baselga, Jose
Marangoni, Elisabetta
Welm, Alana L.
Aparicio, Samuel
Serra, Violeta
Garnett, Mathew J.
Caldas, Carlos
A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds
title A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds
title_full A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds
title_fullStr A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds
title_full_unstemmed A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds
title_short A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds
title_sort biobank of breast cancer explants with preserved intra-tumor heterogeneity to screen anticancer compounds
topic Resource
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5037319/
https://www.ncbi.nlm.nih.gov/pubmed/27641504
http://dx.doi.org/10.1016/j.cell.2016.08.041
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