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.
authors.affiliation: Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK.
authors.forename: Alejandra
authors.initials: A
authors.lastname: Bruna
authors.affiliation: Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK.
authors.forename: Oscar M
authors.initials: OM
authors.lastname: Rueda
authors.affiliation: Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK.
authors.forename: Wendy
authors.initials: W
authors.lastname: Greenwood
authors.affiliation: Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK.
authors.forename: Ankita Sati
authors.initials: AS
authors.lastname: Batra
authors.affiliation: Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Callari
authors.affiliation: Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK.
authors.forename: Rajbir Nath
authors.initials: RN
authors.lastname: Batra
authors.affiliation: Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK.
authors.forename: Katherine
authors.initials: K
authors.lastname: Pogrebniak
authors.affiliation: Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK.
authors.forename: Jose
authors.initials: J
authors.lastname: Sandoval
authors.affiliation: Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK.
authors.forename: John W
authors.initials: JW
authors.lastname: Cassidy
authors.affiliation: Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK.
authors.forename: Ana
authors.initials: A
authors.lastname: Tufegdzic-Vidakovic
authors.affiliation: Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK.
authors.forename: Stephen-John
authors.initials: SJ
authors.lastname: Sammut
authors.affiliation: Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK; Cambridge Breast Unit, NIHR Cambridge Biomedical Research Centre and Cambridge Experimental Cancer Medicine Centre at Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 2QQ, UK.
authors.forename: Linda
authors.initials: L
authors.lastname: Jones
authors.affiliation: Cambridge Breast Unit, NIHR Cambridge Biomedical Research Centre and Cambridge Experimental Cancer Medicine Centre at Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 2QQ, UK.
authors.forename: Elena
authors.initials: E
authors.lastname: Provenzano
authors.affiliation: Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK; Cambridge Breast Unit, NIHR Cambridge Biomedical Research Centre and Cambridge Experimental Cancer Medicine Centre at Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 2QQ, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Baird
authors.affiliation: Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Peter
authors.initials: P
authors.lastname: Eirew
authors.affiliation: Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK.
authors.forename: James
authors.initials: J
authors.lastname: Hadfield
authors.affiliation: Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK.
authors.forename: Matthew
authors.initials: M
authors.lastname: Eldridge
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: McLaren-Douglas
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Barthorpe
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
authors.forename: Howard
authors.initials: H
authors.lastname: Lightfoot
authors.affiliation: DNA Damage Response Biology Area, Oncology IMED, AstraZeneca, Alderley Park, Macclesfield SK10 4TG, UK.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: O'Connor
authors.affiliation: OHSU Knight Cancer Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
authors.forename: Joe
authors.initials: J
authors.lastname: Gray
authors.affiliation: Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Cortes
authors.affiliation: Human Oncology and Pathogenesis Program, Department of Medicine, Memorial Sloan Kettering Cancer Center, NY 10065, USA.
authors.forename: Jose
authors.initials: J
authors.lastname: Baselga
authors.affiliation: Translational Research Department, Institut Curie, 26 rue d'Ulm, Paris 75005, France.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Marangoni
authors.affiliation: Huntsman Cancer Institute, Salt Lake City, UT 84112, USA.
authors.forename: Alana L
authors.initials: AL
authors.lastname: Welm
authors.affiliation: Department of Molecular Oncology, British Columbia Cancer Research Centre, Vancouver, BC V5Z 1L3, Canada.
authors.forename: Samuel
authors.initials: S
authors.lastname: Aparicio
authors.affiliation: Vall d'Hebron Institute of Oncology, 08035 Barcelona, Spain.
authors.forename: Violeta
authors.initials: V
authors.lastname: Serra
authors.affiliation: Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
authors.forename: Mathew J
authors.initials: MJ
authors.lastname: Garnett
authors.affiliation: Department of Oncology and Cancer Research UK Cambridge Institute, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK; Cambridge Breast Unit, NIHR Cambridge Biomedical Research Centre and Cambridge Experimental Cancer Medicine Centre at Cambridge University Hospitals NHS Foundation Trust, Cambridge CB2 2QQ, UK. Electronic address: carlos.caldas@cruk.cam.ac.uk.
authors.forename: Carlos
authors.initials: C
authors.lastname: Caldas
mesh_terms: D000818:Animals; D018070:Biological Specimen Banks; D054316:Biomarkers, Pharmacological; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D057166:High-Throughput Screening Assays; D006801:Humans; D051379:Mice; D000071185:Pharmacogenomic Testing; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D054316:Biomarkers, Pharmacological