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

被引：351

作者：

Bruna, Alejandra ^{[1
,2
]}

Rueda, Oscar M. ^{[1
,2
]}

Greenwood, Wendy ^{[1
,2
]}

Batra, Ankita Sati ^{[1
,2
]}

Callari, Maurizio ^{[1
,2
]}

Batra, Rajbir Nath ^{[1
,2
]}

Pogrebniak, Katherine ^{[1
,2
]}

Sandoval, Jose ^{[1
,2
]}

Cassidy, John W. ^{[1
,2
]}

Tufegdzic-Vidakovic, Ana ^{[1
,2
]}

Sammut, Stephen-John ^{[1
,2
]}

Jones, Linda ^{[1
,2
,3
,4
]}

Provenzano, Elena ^{[3
,4
]}

Baird, Richard ^{[1
,2
,3
,4
]}

Eirew, Peter ^{[5
]}

Hadfield, James ^{[1
,2
]}

Eldridge, Matthew ^{[1
,2
]}

McLaren-Douglas, Anne ^{[6
]}

Barthorpe, Andrew ^{[6
]}

Lightfoot, Howard ^{[6
]}

O'Connor, Mark J. ^{[7
]}

Gray, Joe ^{[8
]}

Cortes, Javier ^{[9
]}

Baselga, Jose ^{[10
]}

Marangoni, Elisabetta ^{[11
]}

Welm, Alana L. ^{[12
]}

Aparicio, Samuel ^{[5
]}

Serra, Violeta ^{[9
]}

Garnett, Mathew J. ^{[6
]}

Caldas, Carlos ^{[1
,2
,3
,4
]}

机构：

[1] Univ Cambridge, Dept Oncol, Cambridge CB2 0RE, England

[2] Univ Cambridge, Canc Res UK Cambridge Inst, Li Ka Shing Ctr, Cambridge CB2 0RE, England

[3] Cambridge Univ Hosp NHS Fdn Trust, NIHR Cambridge Biomed Res Ctr, Cambridge Breast Unit, Cambridge CB2 2QQ, England

[4] Cambridge Univ Hosp NHS Fdn Trust, Cambridge Expt Canc Med Ctr, Cambridge CB2 2QQ, England

[5] British Columbia Canc Res Ctr, Dept Mol Oncol, Vancouver, BC V5Z 1L3, Canada

[6] Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Hinxton CB10 1SA, Cambs, England

[7] AstraZeneca, Oncol IMED, DNA Damage Response Biol Area, Alderley Pk, Macclesfield SK10 4TG, Cheshire, England

[8] Oregon Hlth & Sci Univ, OHSU Knight Canc Inst, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA

[9] Vall dHebron Inst Oncol, Barcelona 08035, Spain

[10] Mem Sloan Kettering Canc Ctr, Dept Med, Human Oncol & Pathogenesis Program, New York, NY 10065 USA

[11] Inst Curie, Translat Res Dept, 26 Rue Ulm, F-75005 Paris, France

[12] Huntsman Canc Inst, Salt Lake City, UT 84112 USA

来源：

CELL | 2016年 / 167卷 / 01期

基金：

英国惠康基金;

关键词：

DRIVEN INTEGRATED CLASSIFICATION; COPY NUMBER ANALYSIS; MUTATIONAL EVOLUTION; DNA-REPAIR; XENOGRAFTS; MODELS; 53BP1; IDENTIFICATION; SENSITIVITY; METASTASIS;

D O I：

10.1016/j.cell.2016.08.041

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：260 / +

页数：37

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