title: Patient-derived xenograft (PDX) models in basic and translational breast cancer research.
abstract: Patient-derived xenograft (PDX) models of a growing spectrum of cancers are rapidly supplanting long-established traditional cell lines as preferred models for conducting basic and translational preclinical research. In breast cancer, to complement the now curated collection of approximately 45 long-established human breast cancer cell lines, a newly formed consortium of academic laboratories, currently from Europe, Australia, and North America, herein summarizes data on over 500 stably transplantable PDX models representing all three clinical subtypes of breast cancer (ER+, HER2+, and "Triple-negative" (TNBC)). Many of these models are well-characterized with respect to genomic, transcriptomic, and proteomic features, metastatic behavior, and treatment response to a variety of standard-of-care and experimental therapeutics. These stably transplantable PDX lines are generally available for dissemination to laboratories conducting translational research, and contact information for each collection is provided. This review summarizes current experiences related to PDX generation across participating groups, efforts to develop data standards for annotation and dissemination of patient clinical information that does not compromise patient privacy, efforts to develop complementary data standards for annotation of PDX characteristics and biology, and progress toward "credentialing" of PDX models as surrogates to represent individual patients for use in preclinical and co-clinical translational research. In addition, this review highlights important unresolved questions, as well as current limitations, that have hampered more efficient generation of PDX lines and more rapid adoption of PDX use in translational breast cancer research.
authors.affiliation: The Lester and Sue Smith Breast Center, Departments of Molecular and Cellular Biology and Radiology, Baylor College of Medicine, Houston,, TX, 77030, USA.
authors.forename: Lacey E
authors.initials: LE
authors.lastname: Dobrolecki
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, 04609, USA.
authors.forename: Susie D
authors.initials: SD
authors.lastname: Airhart
authors.affiliation: Breast Cancer Now Research Unit, Division of Molecular and Clinical Cancer Sciences, Manchester Cancer Research Centre, University of Manchester, Wilmslow Road, Manchester, M21 4QL, UK.
authors.forename: Denis G
authors.initials: DG
authors.lastname: Alferez
authors.affiliation: Department of Pathology and Laboratory Medicine, BC Cancer Agency, 675 W10th Avenue, Vancouver, V6R 3A6, Canada.
authors.forename: Samuel
authors.initials: S
authors.lastname: Aparicio
authors.affiliation: Department of Pathology, University of Kansas Medical Center, |3901 Rainbow Blvd, WHE 1005B, Kansas City, KS, 66160, USA.
authors.forename: Fariba
authors.initials: F
authors.lastname: Behbod
authors.affiliation: Department of Biomedicine, University of Basel, University Hospital Basel, Lab 306, Hebelstrasse 20, CH-4031, Basel, Switzerland.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Bentires-Alj
authors.affiliation: School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), ISREC-Swiss Institute for Experimental Cancer Research, SV2.832 Station 19, 1015, Lausanne, Switzerland.
authors.forename: Cathrin
authors.initials: C
authors.lastname: Brisken
authors.affiliation: The Jackson Laboratory, Bar Harbor, ME, 04609, USA.
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Bult
authors.affiliation: Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
authors.forename: Shirong
authors.initials: S
authors.lastname: Cai
authors.affiliation: Breast Cancer Now Research Unit, Division of Molecular and Clinical Cancer Sciences, Manchester Cancer Research Centre, University of Manchester, Wilmslow Road, Manchester, M21 4QL, UK.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Clarke
authors.affiliation: Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
authors.forename: Heidi
authors.initials: H
authors.lastname: Dowst
authors.affiliation: The Lester and Sue Smith Breast Center, Departments of Molecular and Cellular Biology and Radiology, Baylor College of Medicine, Houston,, TX, 77030, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Ellis
authors.affiliation: Cancer Epigenetics and Biology Program, PEBC, Bellvitge Institute for Biomedical Research, IDIBELL, Av. Gran Via de L'Hospitalet, 199-203, 08908 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Gonzalez-Suarez
authors.affiliation: INSERM U1218, Bergonié Cancer Institute, 229 cours de l'Argonne, 33076, Bordeaux, France.
authors.forename: Richard D
authors.initials: RD
authors.lastname: Iggo
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Kabos
authors.affiliation: Department of Internal Medicine, Washington University, St. Louis, MO, 63130, USA.
authors.forename: Shunqiang
authors.initials: S
authors.lastname: Li
authors.affiliation: Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC, 3052, Australia.|Department of Medicine, The University of Melbourne, Parkville, VIC, 3010, Australia.|Familial Cancer Centre, Royal Melbourne Hospital, Peter MacCallum Cancer Centre, Grattan St, Parkville, VIC, 3050, Australia.
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Lindeman
authors.affiliation: Translational Research Department, Institut Curie, 26, rue d'Ulm, 75005, Paris, France.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Marangoni
authors.affiliation: Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: McCoy
authors.affiliation: Departments of Investigational Cancer Therapeutics and Breast Surgical Oncology, UT M. D. Anderson Cancer Center, Houston, TX, 77030, USA.
authors.forename: Funda
authors.initials: F
authors.lastname: Meric-Bernstam
authors.affiliation: Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Piwnica-Worms
authors.affiliation: Founder and Scientific Advisor, XenTech SA, Genopole, 4 rue Pierre Fontaine, 91000, Evry, France.
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Poupon
authors.affiliation: Director of Experimental Pathology, Department of Pathology, Affiliate Member, Human Oncology and Pathogenesis Program, and Center for Computational Biology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Reis-Filho
authors.affiliation: Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Sartorius
authors.affiliation: School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), ISREC-Swiss Institute for Experimental Cancer Research, SV2.832 Station 19, 1015, Lausanne, Switzerland.
authors.forename: Valentina
authors.initials: V
authors.lastname: Scabia
authors.affiliation: School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), ISREC-Swiss Institute for Experimental Cancer Research, SV2.832 Station 19, 1015, Lausanne, Switzerland.
authors.forename: George
authors.initials: G
authors.lastname: Sflomos
authors.affiliation: Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
authors.forename: Yizheng
authors.initials: Y
authors.lastname: Tu
authors.affiliation: Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC, 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
authors.forename: François
authors.initials: F
authors.lastname: Vaillant
authors.affiliation: Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC, 3052, Australia.|Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Visvader
authors.affiliation: Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.
authors.forename: Alana
authors.initials: A
authors.lastname: Welm
authors.affiliation: Madeline and Sidney Forbes Professor of Oncology, Director, Forbes Institute for Cancer Discovery, NCRC 26-335S, SPC 2800 2800 Plymouth Rd, Ann Arbor, MI, 48109-2800, USA.
authors.forename: Max S
authors.initials: MS
authors.lastname: Wicha
authors.affiliation: The Lester and Sue Smith Breast Center, Departments of Molecular and Cellular Biology and Radiology, Baylor College of Medicine, Houston,, TX, 77030, USA. mtlewis@bcm.edu.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Lewis
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D064593:Heterografts; D006801:Humans; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D057170:Translational Research, Biomedical
keywords: Breast cancer; Immunocompromised/immunodeficient mice; PDX consortium; Patient-derived xenograft; Translational research