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

Alejandra Bruna; Oscar M. Rueda; Wendy Greenwood; Ankita Sati Batra; Maurizio Callari; Rajbir Nath Batra; Katherine Pogrebniak; Jose Sandoval; John W. Cassidy; Ana Tufegdzic-Vidakovic; Stephen John Sammut; Linda Jones; Elena Provenzano; Richard Baird; Peter Eirew; James Hadfield; Matthew Eldridge; Anne McLaren-Douglas; Andrew Barthorpe; Howard Lightfoot; Mark J. O'Connor; Joe Gray; Javier Cortes; Jose Baselga; Elisabetta Marangoni; Alana L. Welm; Samuel Aparicio; Violeta Serra; Mathew J. Garnett; Carlos Caldas

doi:10.1016/j.cell.2016.08.041

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

Alejandra Bruna, Oscar M. Rueda, Wendy Greenwood, Ankita Sati Batra, Maurizio Callari, Rajbir Nath Batra, Katherine Pogrebniak, Jose Sandoval, John W. Cassidy, Ana Tufegdzic-Vidakovic, Stephen John Sammut, Linda Jones, Elena Provenzano, Richard Baird, Peter Eirew, James Hadfield, Matthew Eldridge, Anne McLaren-Douglas, Andrew Barthorpe, Howard LightfootMark J. O'Connor, Joe Gray, Javier Cortes, Jose Baselga, Elisabetta Marangoni, Alana L. Welm, Samuel Aparicio, Violeta Serra, Mathew J. Garnett, Carlos Caldas

Biomedical Engineering

Research output: Contribution to journal › Article › peer-review

310 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	260-274.e22
Journal	Cell
Volume	167
Issue number	1
DOIs	https://doi.org/10.1016/j.cell.2016.08.041
State	Published - Sep 22 2016

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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Bruna, A., Rueda, O. M., Greenwood, W., Batra, A. S., Callari, M., Batra, R. N., Pogrebniak, K., Sandoval, J., Cassidy, J. W., Tufegdzic-Vidakovic, A., Sammut, S. J., Jones, L., Provenzano, E., Baird, R., Eirew, P., Hadfield, J., Eldridge, M., McLaren-Douglas, A., Barthorpe, A., ... Caldas, C. (2016). A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds. Cell, 167(1), 260-274.e22. https://doi.org/10.1016/j.cell.2016.08.041

Bruna, A, Rueda, OM, Greenwood, W, Batra, AS, Callari, M, Batra, RN, Pogrebniak, K, Sandoval, J, Cassidy, JW, Tufegdzic-Vidakovic, A, Sammut, SJ, Jones, L, Provenzano, E, Baird, R, Eirew, P, Hadfield, J, Eldridge, M, McLaren-Douglas, A, Barthorpe, A, Lightfoot, H, O'Connor, MJ, Gray, J, Cortes, J, Baselga, J, Marangoni, E, Welm, AL, Aparicio, S, Serra, V, Garnett, MJ & Caldas, C 2016, 'A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds', Cell, vol. 167, no. 1, pp. 260-274.e22. https://doi.org/10.1016/j.cell.2016.08.041

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

abstract = "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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AU - Callari, Maurizio

AU - Batra, Rajbir Nath

AU - Pogrebniak, Katherine

AU - Sandoval, Jose

AU - Cassidy, John W.

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AU - Barthorpe, Andrew

AU - Lightfoot, Howard

AU - O'Connor, Mark J.

AU - Gray, Joe

AU - Cortes, Javier

AU - Baselga, Jose

AU - Marangoni, Elisabetta

AU - Welm, Alana L.

AU - Aparicio, Samuel

AU - Serra, Violeta

AU - Garnett, Mathew J.

AU - Caldas, Carlos

PY - 2016/9/22

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

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ASJC Scopus subject areas

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