The Oncopig Cancer Model: An Innovative Large Animal Translational Oncology Platform

Kyle M. Schachtschneider, Regina M. Schwind, Jordan Newson, Nickolas Kinachtchouk, Mark Rizko, Nasya Mendoza-Elias, Paul Grippo, Daniel R. Principe, Alex Park, Nana Haahr Overgaard, Gregers Jungersen, Kelly D. Garcia, Ajay V. Maker, Laurie A. Rund, Howard Ozer, Ron C. Gaba, Lawrence B. Schook

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    Abstract

    Despite an improved understanding of cancer molecular biology, immune landscapes, and advancements in cytotoxic, biologic, and immunologic anti-cancer therapeutics, cancer remains a leading cause of death worldwide. More than 8.2 million deaths were attributed to cancer in 2012, and it is anticipated that cancer incidence will continue to rise, with 19.3 million cases expected by 2025. The development and investigation of new diagnostic modalities and innovative therapeutic tools is critical for reducing the global cancer burden. Toward this end, transitional animal models serve a crucial role in bridging the gap between fundamental diagnostic and therapeutic discoveries and human clinical trials. Such animal models offer insights into all aspects of the basic science-clinical translational cancer research continuum (screening, detection, oncogenesis, tumor biology, immunogenicity, therapeutics, and outcomes). To date, however, cancer research progress has been markedly hampered by lack of a genotypically, anatomically, and physiologically relevant large animal model. Without progressive cancer models, discoveries are hindered and cures are improbable. Herein, we describe a transgenic porcine model-the Oncopig Cancer Model (OCM)-as a next-generation large animal platform for the study of hematologic and solid tumor oncology. With mutations in key tumor suppressor and oncogenes, TP53R167H and KRASG12D , the OCM recapitulates transcriptional hallmarks of human disease while also exhibiting clinically relevant histologic and genotypic tumor phenotypes. Moreover, as obesity rates increase across the global population, cancer patients commonly present clinically with multiple comorbid conditions. Due to the effects of these comorbidities on patient management, therapeutic strategies, and clinical outcomes, an ideal animal model should develop cancer on the background of representative comorbid conditions (tumor macro- and microenvironments). As observed in clinical practice, liver cirrhosis frequently precedes development of primary liver cancer or hepatocellular carcinoma. The OCM has the capacity to develop tumors in combination with such relevant comorbidities. Furthermore, studies on the tumor microenvironment demonstrate similarities between OCM and human cancer genomic landscapes. This review highlights the potential of this and other large animal platforms as transitional models to bridge the gap between basic research and clinical practice.
    Original languageEnglish
    Article number190
    JournalFrontiers in Oncology
    Volume7
    DOIs
    Publication statusPublished - 2017

    Bibliographical note

    This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).

    Keywords

    • Cancer models
    • Clinical needs
    • Oncology
    • Oncopig
    • Pigs
    • Translational medicine

    Cite this

    Schachtschneider, K. M., Schwind, R. M., Newson, J., Kinachtchouk, N., Rizko, M., Mendoza-Elias, N., ... Schook, L. B. (2017). The Oncopig Cancer Model: An Innovative Large Animal Translational Oncology Platform. Frontiers in Oncology, 7, [190]. https://doi.org/10.3389/fonc.2017.00190
    Schachtschneider, Kyle M. ; Schwind, Regina M. ; Newson, Jordan ; Kinachtchouk, Nickolas ; Rizko, Mark ; Mendoza-Elias, Nasya ; Grippo, Paul ; Principe, Daniel R. ; Park, Alex ; Overgaard, Nana Haahr ; Jungersen, Gregers ; Garcia, Kelly D. ; Maker, Ajay V. ; Rund, Laurie A. ; Ozer, Howard ; Gaba, Ron C. ; Schook, Lawrence B. / The Oncopig Cancer Model: An Innovative Large Animal Translational Oncology Platform. In: Frontiers in Oncology. 2017 ; Vol. 7.
    @article{7f2b5904dc7e4e58888378c65e5c7238,
    title = "The Oncopig Cancer Model: An Innovative Large Animal Translational Oncology Platform",
    abstract = "Despite an improved understanding of cancer molecular biology, immune landscapes, and advancements in cytotoxic, biologic, and immunologic anti-cancer therapeutics, cancer remains a leading cause of death worldwide. More than 8.2 million deaths were attributed to cancer in 2012, and it is anticipated that cancer incidence will continue to rise, with 19.3 million cases expected by 2025. The development and investigation of new diagnostic modalities and innovative therapeutic tools is critical for reducing the global cancer burden. Toward this end, transitional animal models serve a crucial role in bridging the gap between fundamental diagnostic and therapeutic discoveries and human clinical trials. Such animal models offer insights into all aspects of the basic science-clinical translational cancer research continuum (screening, detection, oncogenesis, tumor biology, immunogenicity, therapeutics, and outcomes). To date, however, cancer research progress has been markedly hampered by lack of a genotypically, anatomically, and physiologically relevant large animal model. Without progressive cancer models, discoveries are hindered and cures are improbable. Herein, we describe a transgenic porcine model-the Oncopig Cancer Model (OCM)-as a next-generation large animal platform for the study of hematologic and solid tumor oncology. With mutations in key tumor suppressor and oncogenes, TP53R167H and KRASG12D , the OCM recapitulates transcriptional hallmarks of human disease while also exhibiting clinically relevant histologic and genotypic tumor phenotypes. Moreover, as obesity rates increase across the global population, cancer patients commonly present clinically with multiple comorbid conditions. Due to the effects of these comorbidities on patient management, therapeutic strategies, and clinical outcomes, an ideal animal model should develop cancer on the background of representative comorbid conditions (tumor macro- and microenvironments). As observed in clinical practice, liver cirrhosis frequently precedes development of primary liver cancer or hepatocellular carcinoma. The OCM has the capacity to develop tumors in combination with such relevant comorbidities. Furthermore, studies on the tumor microenvironment demonstrate similarities between OCM and human cancer genomic landscapes. This review highlights the potential of this and other large animal platforms as transitional models to bridge the gap between basic research and clinical practice.",
    keywords = "Cancer models, Clinical needs, Oncology, Oncopig, Pigs, Translational medicine",
    author = "Schachtschneider, {Kyle M.} and Schwind, {Regina M.} and Jordan Newson and Nickolas Kinachtchouk and Mark Rizko and Nasya Mendoza-Elias and Paul Grippo and Principe, {Daniel R.} and Alex Park and Overgaard, {Nana Haahr} and Gregers Jungersen and Garcia, {Kelly D.} and Maker, {Ajay V.} and Rund, {Laurie A.} and Howard Ozer and Gaba, {Ron C.} and Schook, {Lawrence B.}",
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    year = "2017",
    doi = "10.3389/fonc.2017.00190",
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    volume = "7",
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    Schachtschneider, KM, Schwind, RM, Newson, J, Kinachtchouk, N, Rizko, M, Mendoza-Elias, N, Grippo, P, Principe, DR, Park, A, Overgaard, NH, Jungersen, G, Garcia, KD, Maker, AV, Rund, LA, Ozer, H, Gaba, RC & Schook, LB 2017, 'The Oncopig Cancer Model: An Innovative Large Animal Translational Oncology Platform', Frontiers in Oncology, vol. 7, 190. https://doi.org/10.3389/fonc.2017.00190

    The Oncopig Cancer Model: An Innovative Large Animal Translational Oncology Platform. / Schachtschneider, Kyle M.; Schwind, Regina M.; Newson, Jordan; Kinachtchouk, Nickolas; Rizko, Mark; Mendoza-Elias, Nasya; Grippo, Paul; Principe, Daniel R.; Park, Alex; Overgaard, Nana Haahr; Jungersen, Gregers; Garcia, Kelly D.; Maker, Ajay V.; Rund, Laurie A.; Ozer, Howard; Gaba, Ron C.; Schook, Lawrence B.

    In: Frontiers in Oncology, Vol. 7, 190, 2017.

    Research output: Contribution to journalJournal articleResearchpeer-review

    TY - JOUR

    T1 - The Oncopig Cancer Model: An Innovative Large Animal Translational Oncology Platform

    AU - Schachtschneider, Kyle M.

    AU - Schwind, Regina M.

    AU - Newson, Jordan

    AU - Kinachtchouk, Nickolas

    AU - Rizko, Mark

    AU - Mendoza-Elias, Nasya

    AU - Grippo, Paul

    AU - Principe, Daniel R.

    AU - Park, Alex

    AU - Overgaard, Nana Haahr

    AU - Jungersen, Gregers

    AU - Garcia, Kelly D.

    AU - Maker, Ajay V.

    AU - Rund, Laurie A.

    AU - Ozer, Howard

    AU - Gaba, Ron C.

    AU - Schook, Lawrence B.

    N1 - This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).

    PY - 2017

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    N2 - Despite an improved understanding of cancer molecular biology, immune landscapes, and advancements in cytotoxic, biologic, and immunologic anti-cancer therapeutics, cancer remains a leading cause of death worldwide. More than 8.2 million deaths were attributed to cancer in 2012, and it is anticipated that cancer incidence will continue to rise, with 19.3 million cases expected by 2025. The development and investigation of new diagnostic modalities and innovative therapeutic tools is critical for reducing the global cancer burden. Toward this end, transitional animal models serve a crucial role in bridging the gap between fundamental diagnostic and therapeutic discoveries and human clinical trials. Such animal models offer insights into all aspects of the basic science-clinical translational cancer research continuum (screening, detection, oncogenesis, tumor biology, immunogenicity, therapeutics, and outcomes). To date, however, cancer research progress has been markedly hampered by lack of a genotypically, anatomically, and physiologically relevant large animal model. Without progressive cancer models, discoveries are hindered and cures are improbable. Herein, we describe a transgenic porcine model-the Oncopig Cancer Model (OCM)-as a next-generation large animal platform for the study of hematologic and solid tumor oncology. With mutations in key tumor suppressor and oncogenes, TP53R167H and KRASG12D , the OCM recapitulates transcriptional hallmarks of human disease while also exhibiting clinically relevant histologic and genotypic tumor phenotypes. Moreover, as obesity rates increase across the global population, cancer patients commonly present clinically with multiple comorbid conditions. Due to the effects of these comorbidities on patient management, therapeutic strategies, and clinical outcomes, an ideal animal model should develop cancer on the background of representative comorbid conditions (tumor macro- and microenvironments). As observed in clinical practice, liver cirrhosis frequently precedes development of primary liver cancer or hepatocellular carcinoma. The OCM has the capacity to develop tumors in combination with such relevant comorbidities. Furthermore, studies on the tumor microenvironment demonstrate similarities between OCM and human cancer genomic landscapes. This review highlights the potential of this and other large animal platforms as transitional models to bridge the gap between basic research and clinical practice.

    AB - Despite an improved understanding of cancer molecular biology, immune landscapes, and advancements in cytotoxic, biologic, and immunologic anti-cancer therapeutics, cancer remains a leading cause of death worldwide. More than 8.2 million deaths were attributed to cancer in 2012, and it is anticipated that cancer incidence will continue to rise, with 19.3 million cases expected by 2025. The development and investigation of new diagnostic modalities and innovative therapeutic tools is critical for reducing the global cancer burden. Toward this end, transitional animal models serve a crucial role in bridging the gap between fundamental diagnostic and therapeutic discoveries and human clinical trials. Such animal models offer insights into all aspects of the basic science-clinical translational cancer research continuum (screening, detection, oncogenesis, tumor biology, immunogenicity, therapeutics, and outcomes). To date, however, cancer research progress has been markedly hampered by lack of a genotypically, anatomically, and physiologically relevant large animal model. Without progressive cancer models, discoveries are hindered and cures are improbable. Herein, we describe a transgenic porcine model-the Oncopig Cancer Model (OCM)-as a next-generation large animal platform for the study of hematologic and solid tumor oncology. With mutations in key tumor suppressor and oncogenes, TP53R167H and KRASG12D , the OCM recapitulates transcriptional hallmarks of human disease while also exhibiting clinically relevant histologic and genotypic tumor phenotypes. Moreover, as obesity rates increase across the global population, cancer patients commonly present clinically with multiple comorbid conditions. Due to the effects of these comorbidities on patient management, therapeutic strategies, and clinical outcomes, an ideal animal model should develop cancer on the background of representative comorbid conditions (tumor macro- and microenvironments). As observed in clinical practice, liver cirrhosis frequently precedes development of primary liver cancer or hepatocellular carcinoma. The OCM has the capacity to develop tumors in combination with such relevant comorbidities. Furthermore, studies on the tumor microenvironment demonstrate similarities between OCM and human cancer genomic landscapes. This review highlights the potential of this and other large animal platforms as transitional models to bridge the gap between basic research and clinical practice.

    KW - Cancer models

    KW - Clinical needs

    KW - Oncology

    KW - Oncopig

    KW - Pigs

    KW - Translational medicine

    U2 - 10.3389/fonc.2017.00190

    DO - 10.3389/fonc.2017.00190

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    C2 - 28879168

    VL - 7

    JO - Frontiers in Oncology

    JF - Frontiers in Oncology

    SN - 2234-943X

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    ER -

    Schachtschneider KM, Schwind RM, Newson J, Kinachtchouk N, Rizko M, Mendoza-Elias N et al. The Oncopig Cancer Model: An Innovative Large Animal Translational Oncology Platform. Frontiers in Oncology. 2017;7. 190. https://doi.org/10.3389/fonc.2017.00190