A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds.
Embargo End Date
ICR Authors
Authors
Bruna, A
Rueda, OM
Greenwood, W
Batra, AS
Callari, M
Batra, RN
Pogrebniak, K
Sandoval, J
Cassidy, JW
Tufegdzic-Vidakovic, A
Sammut, S-J
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
Rueda, OM
Greenwood, W
Batra, AS
Callari, M
Batra, RN
Pogrebniak, K
Sandoval, J
Cassidy, JW
Tufegdzic-Vidakovic, A
Sammut, S-J
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
Document Type
Journal Article
Date
2016-09-22
Date Accepted
2016-08-18
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.
Citation
Cell, 2016, 167 (1), pp. 260 - 274.e22
Source Title
Publisher
CELL PRESS
ISSN
0092-8674
eISSN
1097-4172
Collections
Research Team
Preclinical Modelling of Paediatric Cancer Evolution