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

Research output: Contribution to journalArticle

142 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 languageEnglish (US)
Pages (from-to)260-274.e22
JournalCell
Volume167
Issue number1
DOIs
StatePublished - Sep 22 2016

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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