Cancer and Metastasis Reviews

, Volume 35, Issue 4, pp 547–573 | Cite as

Patient-derived xenograft (PDX) models in basic and translational breast cancer research

  • Lacey E. Dobrolecki
  • Susie D. Airhart
  • Denis G. Alferez
  • Samuel Aparicio
  • Fariba Behbod
  • Mohamed Bentires-Alj
  • Cathrin Brisken
  • Carol J. Bult
  • Shirong Cai
  • Robert B. Clarke
  • Heidi Dowst
  • Matthew J. Ellis
  • Eva Gonzalez-Suarez
  • Richard D. Iggo
  • Peter Kabos
  • Shunqiang Li
  • Geoffrey J. Lindeman
  • Elisabetta Marangoni
  • Aaron McCoy
  • Funda Meric-Bernstam
  • Helen Piwnica-Worms
  • Marie-France Poupon
  • Jorge Reis-Filho
  • Carol A. Sartorius
  • Valentina Scabia
  • George Sflomos
  • Yizheng Tu
  • François Vaillant
  • Jane E. Visvader
  • Alana Welm
  • Max S. Wicha
  • Michael T. Lewis


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.


Patient-derived xenograft Breast cancer Immunocompromised/immunodeficient mice Translational research PDX consortium 



Samuel Aparicio—Supported by the BC Cancer Foundation, Canadian Breast Cancer Foundation, CIHR, Canadian Foundation for Innovation, Stand Up to Cancer Canada, Canadian Cancer Research Institute, and Terry Fox Research Institute

Fariba Behbod—Supported by R01-NIH/NCI-R01CA172764, NIH/NCI-R21CA187890, AACR-Breast Cancer Research Foundation-2014 Translational Breast Cancer Research, and NIH/NCI-R21CA185460

Cathrin Brisken—The research leading to these results has received support from the Swiss Cancer League, the SNF, and the Innovative Medicines Initiative Joint Undertaking (grant agreement no. 115188) for the PREDECT consortium ( resources composed of financial contribution from EU-FP7 and EFPIA companies in kind contribution. The Web address of the Innovative Medicines Initiative is

Carol J. Bult—This work was supported in part by the Maine Cancer Foundation, The Jackson Laboratory Director’s Innovation Fund, and JAX Cancer Center grant P30 CA034196.

Matthew Ellis—Dr. Ellis is a McNair Medical Institute Scholar and a CPRIT Established Investigator (CPRIT RR140033).

Robert Clarke and Denis Alferez—This work was funded by Cancer Research UK and Breast Cancer Now. We would like to thank all patients who donated tissue to this study and the Manchester Cancer Research Centre Biobank for consenting patients and collecting tissue.

Eva Gonzalez-Suarez—This work was supported in part by grants to Eva González Suárez by the Spanish Ministry of Economy and Competitivity MINECO and from the ISCIII (SAF2008-01975, SAF2011-22893, SAF2014-55997), PIE13/00022, co-funded by FEDER funds/European Regional Development Fund (ERDF—a way to build Europe), by a Career Catalyst grant from the Susan Komen Foundation and by institutional funds provided by the Generalitat de Catalunya.

Richard Iggo—This work was supported by the “Fondation pour la lutte contre le cancer et pour des recherches medico-biologiques,” the INCa-DGOS-INSERM 6046 SIRIC BRIO grant, and the French Cancer League (Comité de la Charente Maritime).

Peter Kabos—NIH grant CA164048, Grohne Cancer Research Fund

Michael T. Lewis—This work was supported in part by the Breast Cancer Research Foundation, the Emma Jacobs Clinical Breast Cancer Fund, the Susan G. Komen Foundation, Cancer Fighters of Houston, BCM Cancer Center grant P30 CA125123, BCM Breast Cancer SPORE P50 CA50183, NIH/NCI grant R01 CA112305, and NIH/NCI grant U54 CA149196. The authors also acknowledge the joint participation by Diana Henry Helis Medical Research Foundation through its direct engagement in the continuous active conduct of medical research in conjunction with Baylor College of Medicine and its “Blood-borne BioMarkers for Detection of Breast Cancer” Program.

Shunqiang Li—Susan G. Komen for the Cure (BCTR0707808, KG090422, and PG12220321), Breast Cancer Research Foundation, CTSA grant UL1 RR024992, and The Fashion Footwear Charitable Foundation, Inc.

Geoffrey J. Lindeman and Jane E. Visvader—Received funding support from the Australian National Health and Medical Research Council (NHMRC; 1016701, 1040978, 1086727, 1085191); NHMRC Independent Research Institute Infrastructure Support Scheme (IRIISS) (to WEHI); the Victorian State Government through the Victorian Cancer Agency and Operational Infrastructure Support; the National Breast Cancer Foundation (Australia); the Cancer Therapeutics CRC; and the Australian Cancer Research Foundation. G.J.L. is supported by an NHMRC Research Fellowship (1078730); J.E.V. is supported by an NHMRC Australia Fellowship (1037230).

Funda Meric-Bernstam—MD Anderson Moon Shots funds and Nellie B. Connally Breast Cancer Research Endowment

Helen Piwnica-Worms—This work was supported in part by the Cazalot Breast Cancer Model Resource, The Susan G. Komen Foundation, and The Cancer Prevention and Research Institute of Texas (CPRIT) RP150148.

Jorge Reis-Filho—Research reported in this publication was supported in part by a grant from the Breast Cancer Research Foundation and a Cancer Center Support grant of the National Institutes of Health/National Cancer Institute (grant no. P30CA008748). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Carol Sartorius—NIH grant CA140985.

Alana Welm—The Noreen Fraser Foundation, METAvivor Foundation, AACR Susan G. Komen Career Catalyst award, DOD Breast Cancer Research Program grants W81XWH-08-1-0109 and BC112623, and NIH/NCI grants 1R01CA166422 and 1R01CA173903

Max Wicha—R35: CA129765; RO1 CA101860, Komen for the Cure Promise grant, and Breast Cancer Research Foundation grant

Compliance with ethical standards

Competing financial interests

Lacey E. Dobrolecki: Compensated part-time employee of StemMed, Ltd.

Susie D. Airhart: No competing financial interests.

Denis G. Alferez: No competing financial interests.

Samuel Aparicio: No competing financial interests.

Fariba Behbod: No competing financial interests.

Mohamed Bentires-Alj: No competing financial interests.

Cathrin Brisken: No competing financial interests.

Carol J. Bult: No competing financial interests.

Robert B. Clarke: No competing financial interests.

Matthew J. Ellis: Receives income from Washington University in St. Louis which has licensed the WHIM series of breast PDX for commercial distribution.

Eva Gonzalez Suarez: No competing financial interests.

Richard Iggo: No competing financial interests.

Peter Kabos: No competing financial interests.

Michael T. Lewis: Receives income from Baylor College of Medicine which has licensed the BCM series of breast PDX for commercial use. Founder and limited partner in StemMed Ltd. and a Manager in StemMed Holdings LLC.

Shunqiang Li: Receives income from Washington University in St. Louis which has licensed the WHIM series of breast PDX for commercial distribution.

Geoffrey J. Lindeman: No competing financial interests.

Elisabetta.Marangoni: No competing financial interests.

Funda Meric-Bernstam: No competing financial interests.

Helen Piwnica-Worms: No competing financial interests.

Marie-France Poupon: Founder and Scientific Advisor to XenTech SA, Genopole, 4 rue Pierre Fontaine, 91000 Evry, France.

Jorge Reis-Filho: No competing financial interests.

Carol Sartorius: No competing financial interests.

Valentina Scabia: No competing financial interests.

George Sflomos: No competing financial interests.

François Vaillant: No competing financial interests.

Jane Visvader: No competing financial interests.

Alana Welm: Receives income if the University of Utah licenses the PDX models for commercial use.

Max S. Wicha: No competing financial interests.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Lacey E. Dobrolecki
    • 1
  • Susie D. Airhart
    • 2
  • Denis G. Alferez
    • 3
  • Samuel Aparicio
    • 4
  • Fariba Behbod
    • 5
  • Mohamed Bentires-Alj
    • 6
  • Cathrin Brisken
    • 7
  • Carol J. Bult
    • 2
  • Shirong Cai
    • 8
  • Robert B. Clarke
    • 3
  • Heidi Dowst
    • 9
  • Matthew J. Ellis
    • 1
  • Eva Gonzalez-Suarez
    • 10
  • Richard D. Iggo
    • 11
  • Peter Kabos
    • 12
  • Shunqiang Li
    • 13
  • Geoffrey J. Lindeman
    • 14
    • 15
    • 16
  • Elisabetta Marangoni
    • 17
  • Aaron McCoy
    • 8
  • Funda Meric-Bernstam
    • 18
  • Helen Piwnica-Worms
    • 8
  • Marie-France Poupon
    • 19
  • Jorge Reis-Filho
    • 20
  • Carol A. Sartorius
    • 21
  • Valentina Scabia
    • 7
  • George Sflomos
    • 7
  • Yizheng Tu
    • 8
  • François Vaillant
    • 14
    • 22
  • Jane E. Visvader
    • 14
    • 22
  • Alana Welm
    • 23
  • Max S. Wicha
    • 24
  • Michael T. Lewis
    • 1
  1. 1.The Lester and Sue Smith Breast Center, Departments of Molecular and Cellular Biology and RadiologyBaylor College of MedicineHouston,USA
  2. 2.The Jackson LaboratoryBar HarborUSA
  3. 3.Breast Cancer Now Research Unit, Division of Molecular and Clinical Cancer Sciences, Manchester Cancer Research CentreUniversity of ManchesterManchesterUK
  4. 4.Department of Pathology and Laboratory MedicineBC Cancer AgencyVancouverCanada
  5. 5.Department of PathologyUniversity of Kansas Medical CenterKansas CityUSA
  6. 6.Department of BiomedicineUniversity of Basel, University Hospital BaselBaselSwitzerland
  7. 7.School of Life SciencesEcole Polytechnique Fédérale de Lausanne (EPFL), ISREC—Swiss Institute for Experimental Cancer ResearchLausanneSwitzerland
  8. 8.Department of Experimental Radiation OncologyUniversity of Texas MD Anderson Cancer CenterHoustonUSA
  9. 9.Dan L. Duncan Cancer CenterBaylor College of MedicineHoustonUSA
  10. 10.Cancer Epigenetics and Biology ProgramPEBC, Bellvitge Institute for Biomedical Research, IDIBELL, Av. Gran Via de L’HospitaletBarcelonaSpain
  11. 11.INSERM U1218Bergonié Cancer InstituteBordeauxFrance
  12. 12.Division of Medical Oncology, Department of MedicineUniversity of Colorado Anschutz Medical CampusAuroraUSA
  13. 13.Department of Internal MedicineWashington UniversitySt. LouisUSA
  14. 14.Stem Cells and Cancer DivisionWalter and Eliza Hall Institute of Medical ResearchParkvilleAustralia
  15. 15.Department of MedicineThe University of MelbourneParkvilleAustralia
  16. 16.Familial Cancer CentreRoyal Melbourne Hospital, Peter MacCallum Cancer CentreParkvilleAustralia
  17. 17.Translational Research DepartmentInstitut CurieParisFrance
  18. 18.Departments of Investigational Cancer Therapeutics and Breast Surgical OncologyUT M. D. Anderson Cancer CenterHoustonUSA
  19. 19.Founder and Scientific AdvisorXenTech SA, GenopoleEvryFrance
  20. 20.Director of Experimental Pathology, Department of Pathology, Affiliate Member, Human Oncology and Pathogenesis Program, and Center for Computational BiologyMemorial Sloan Kettering Cancer CenterNew YorkUSA
  21. 21.Department of PathologyUniversity of Colorado Anschutz Medical CampusAuroraUSA
  22. 22.Department of Medical BiologyUniversity of MelbourneParkvilleAustralia
  23. 23.Huntsman Cancer InstituteUniversity of UtahSalt Lake CityUSA
  24. 24.Madeline and Sidney Forbes Professor of Oncology, DirectorForbes Institute for Cancer DiscoveryAnn ArborUSA

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