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

Lacey E Dobrolecki¹, Susie D Airhart², Denis G Alferez³, Samuel Aparicio⁴, Fariba Behbod⁵, Mohamed Bentires-Alj⁶, Cathrin Brisken⁷, Carol J Bult², Shirong Cai⁸, Robert B Clarke³, Heidi Dowst⁹, Matthew J Ellis¹, Eva Gonzalez-Suarez¹⁰, Richard D Iggo¹¹, Peter Kabos¹², Shunqiang Li¹³, Geoffrey J Lindeman^{14

15

16}, Elisabetta Marangoni¹⁷, Aaron McCoy⁸, Funda Meric-Bernstam¹⁸, Helen Piwnica-Worms⁸, Marie-France Poupon¹⁹, Jorge Reis-Filho²⁰, Carol A Sartorius²¹, Valentina Scabia⁷, George Sflomos⁷, Yizheng Tu⁸, François Vaillant^{14

22}, Jane E Visvader^{14

22}, Alana Welm²³, Max S Wicha²⁴, Michael T Lewis²⁵

Affiliations

¹ The Lester and Sue Smith Breast Center, Departments of Molecular and Cellular Biology and Radiology, Baylor College of Medicine, Houston,, TX, 77030, USA.
² The Jackson Laboratory, Bar Harbor, ME, 04609, USA.
³ 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.
⁴ Department of Pathology and Laboratory Medicine, BC Cancer Agency, 675 W10th Avenue, Vancouver, V6R 3A6, Canada.
⁵ Department of Pathology, University of Kansas Medical Center, |3901 Rainbow Blvd, WHE 1005B, Kansas City, KS, 66160, USA.
⁶ Department of Biomedicine, University of Basel, University Hospital Basel, Lab 306, Hebelstrasse 20, CH-4031, Basel, Switzerland.
⁷ School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), ISREC-Swiss Institute for Experimental Cancer Research, SV2.832 Station 19, 1015, Lausanne, Switzerland.
⁸ Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
⁹ Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
¹⁰ 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.
¹¹ INSERM U1218, Bergonié Cancer Institute, 229 cours de l'Argonne, 33076, Bordeaux, France.
¹² Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
¹³ Department of Internal Medicine, Washington University, St. Louis, MO, 63130, USA.
¹⁴ Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC, 3052, Australia.
¹⁵ Department of Medicine, The University of Melbourne, Parkville, VIC, 3010, Australia.
¹⁶ Familial Cancer Centre, Royal Melbourne Hospital, Peter MacCallum Cancer Centre, Grattan St, Parkville, VIC, 3050, Australia.
¹⁷ Translational Research Department, Institut Curie, 26, rue d'Ulm, 75005, Paris, France.
¹⁸ Departments of Investigational Cancer Therapeutics and Breast Surgical Oncology, UT M. D. Anderson Cancer Center, Houston, TX, 77030, USA.
¹⁹ Founder and Scientific Advisor, XenTech SA, Genopole, 4 rue Pierre Fontaine, 91000, Evry, France.
²⁰ 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.
²¹ Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
²² Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
²³ Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.
²⁴ 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.
²⁵ 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.

PMID: 28025748
PMCID: PMC5396460
DOI: 10.1007/s10555-016-9653-x

Review

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

Lacey E Dobrolecki et al. Cancer Metastasis Rev. 2016 Dec.

. 2016 Dec;35(4):547-573.

doi: 10.1007/s10555-016-9653-x.

Authors

Affiliations

¹ The Lester and Sue Smith Breast Center, Departments of Molecular and Cellular Biology and Radiology, Baylor College of Medicine, Houston,, TX, 77030, USA.
² The Jackson Laboratory, Bar Harbor, ME, 04609, USA.
³ 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.
⁴ Department of Pathology and Laboratory Medicine, BC Cancer Agency, 675 W10th Avenue, Vancouver, V6R 3A6, Canada.
⁵ Department of Pathology, University of Kansas Medical Center, |3901 Rainbow Blvd, WHE 1005B, Kansas City, KS, 66160, USA.
⁶ Department of Biomedicine, University of Basel, University Hospital Basel, Lab 306, Hebelstrasse 20, CH-4031, Basel, Switzerland.
⁷ School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), ISREC-Swiss Institute for Experimental Cancer Research, SV2.832 Station 19, 1015, Lausanne, Switzerland.
⁸ Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
⁹ Dan L. Duncan Cancer Center, Baylor College of Medicine, Houston, TX, 77030, USA.
¹⁰ 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.
¹¹ INSERM U1218, Bergonié Cancer Institute, 229 cours de l'Argonne, 33076, Bordeaux, France.
¹² Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
¹³ Department of Internal Medicine, Washington University, St. Louis, MO, 63130, USA.
¹⁴ Stem Cells and Cancer Division, Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC, 3052, Australia.
¹⁵ Department of Medicine, The University of Melbourne, Parkville, VIC, 3010, Australia.
¹⁶ Familial Cancer Centre, Royal Melbourne Hospital, Peter MacCallum Cancer Centre, Grattan St, Parkville, VIC, 3050, Australia.
¹⁷ Translational Research Department, Institut Curie, 26, rue d'Ulm, 75005, Paris, France.
¹⁸ Departments of Investigational Cancer Therapeutics and Breast Surgical Oncology, UT M. D. Anderson Cancer Center, Houston, TX, 77030, USA.
¹⁹ Founder and Scientific Advisor, XenTech SA, Genopole, 4 rue Pierre Fontaine, 91000, Evry, France.
²⁰ 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.
²¹ Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
²² Department of Medical Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
²³ Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT, 84112, USA.
²⁴ 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.
²⁵ 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.

PMID: 28025748
PMCID: PMC5396460
DOI: 10.1007/s10555-016-9653-x

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.

Keywords: Breast cancer; Immunocompromised/immunodeficient mice; PDX consortium; Patient-derived xenograft; Translational research.

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References

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

Affiliations

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

Authors

Affiliations

Abstract

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

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Medical

Research Materials

Miscellaneous