A living biobank of matched pairs of patient-derived xenografts and organoids for cancer pharmacology

Patient-derived tumor xenograft (PDX)/organoid (PDO), driven by cancer stem cells (CSC), are considered the most predictive models for translational oncology. Large PDX collections reflective of patient populations have been created and used extensively to test various investigational therapies, inc...

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Published inPloS one Vol. 18; no. 1; p. e0279821
Main Authors Xu, Xiaoxi, Kumari, Rajendra, Zhou, Jun, Chen, Jing, Mao, Binchen, Wang, Jingjing, Zheng, Meiling, Tu, Xiaolong, An, Xiaoyu, Chen, Xiaobo, Zhang, Likun, Tian, Xiaoli, Wang, Haojie, Dong, Xin, Bao, Zhengzheng, Guo, Sheng, Ouyang, Xuesong, Shang, Limei, Wang, Fei, Yan, Xuefei, Zhang, Rui, Vries, Robert G. J., Clevers, Hans, Li, Qi-Xiang
Format Journal Article
LanguageEnglish
Published United States Public Library of Science 05.01.2023
Public Library of Science (PLoS)
Subjects
Animals
Antimitotic agents
Antineoplastic agents
Antineoplastic Agents - pharmacology
Biobanks
Biological Specimen Banks
Biological specimens
Cancer
Clinical trials
Collections and collecting
Colorectal cancer
Disease Models, Animal
Drug dosages
Gastric cancer
Genomics
Heterografts
High-throughput screening
Histopathology
Humans
Immune system
In vivo methods and tests
Laboratory animals
Lead compounds
Liver cancer
Medicine and Health Sciences
Neoplasms - drug therapy
Neoplasms - genetics
Neoplasms - pathology
Oncology, Experimental
Organoids
Pharmacology
Prediction models
R&D
Research & development
Research and Analysis Methods
Stem cells
Tissue banks
Tumors
Xenograft Model Antitumor Assays
Xenografts
Xenotransplantation
China
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Abstract Patient-derived tumor xenograft (PDX)/organoid (PDO), driven by cancer stem cells (CSC), are considered the most predictive models for translational oncology. Large PDX collections reflective of patient populations have been created and used extensively to test various investigational therapies, including population-trials as surrogate subjects in vivo . PDOs are recognized as in vitro surrogates for patients amenable for high-throughput screening (HTS). We have built a biobank of carcinoma PDX-derived organoids (PDXOs) by converting an existing PDX library and confirmed high degree of similarities between PDXOs and parental PDXs in genomics, histopathology and pharmacology, suggesting “biological equivalence or interchangeability” between the two. Here we demonstrate the applications of PDXO biobank for HTS “matrix” screening for both lead compounds and indications, immune cell co-cultures for immune-therapies and engineering enables in vitro/in vivo imaging. This large biobank of >550 matched pairs of PDXs/PDXOs across different cancers could become powerful tools for the future cancer drug discovery.
AbstractList Patient-derived tumor xenograft (PDX)/organoid (PDO), driven by cancer stem cells (CSC), are considered the most predictive models for translational oncology. Large PDX collections reflective of patient populations have been created and used extensively to test various investigational therapies, including population-trials as surrogate subjects in vivo. PDOs are recognized as in vitro surrogates for patients amenable for high-throughput screening (HTS). We have built a biobank of carcinoma PDX-derived organoids (PDXOs) by converting an existing PDX library and confirmed high degree of similarities between PDXOs and parental PDXs in genomics, histopathology and pharmacology, suggesting "biological equivalence or interchangeability" between the two. Here we demonstrate the applications of PDXO biobank for HTS "matrix" screening for both lead compounds and indications, immune cell co-cultures for immune-therapies and engineering enables in vitro/in vivo imaging. This large biobank of >550 matched pairs of PDXs/PDXOs across different cancers could become powerful tools for the future cancer drug discovery.Patient-derived tumor xenograft (PDX)/organoid (PDO), driven by cancer stem cells (CSC), are considered the most predictive models for translational oncology. Large PDX collections reflective of patient populations have been created and used extensively to test various investigational therapies, including population-trials as surrogate subjects in vivo. PDOs are recognized as in vitro surrogates for patients amenable for high-throughput screening (HTS). We have built a biobank of carcinoma PDX-derived organoids (PDXOs) by converting an existing PDX library and confirmed high degree of similarities between PDXOs and parental PDXs in genomics, histopathology and pharmacology, suggesting "biological equivalence or interchangeability" between the two. Here we demonstrate the applications of PDXO biobank for HTS "matrix" screening for both lead compounds and indications, immune cell co-cultures for immune-therapies and engineering enables in vitro/in vivo imaging. This large biobank of >550 matched pairs of PDXs/PDXOs across different cancers could become powerful tools for the future cancer drug discovery.
Patient-derived tumor xenograft (PDX)/organoid (PDO), driven by cancer stem cells (CSC), are considered the most predictive models for translational oncology. Large PDX collections reflective of patient populations have been created and used extensively to test various investigational therapies, including population-trials as surrogate subjects in vivo. PDOs are recognized as in vitro surrogates for patients amenable for high-throughput screening (HTS). We have built a biobank of carcinoma PDX-derived organoids (PDXOs) by converting an existing PDX library and confirmed high degree of similarities between PDXOs and parental PDXs in genomics, histopathology and pharmacology, suggesting "biological equivalence or interchangeability" between the two. Here we demonstrate the applications of PDXO biobank for HTS "matrix" screening for both lead compounds and indications, immune cell co-cultures for immune-therapies and engineering enables in vitro/in vivo imaging. This large biobank of >550 matched pairs of PDXs/PDXOs across different cancers could become powerful tools for the future cancer drug discovery.
Patient-derived tumor xenograft (PDX)/organoid (PDO), driven by cancer stem cells (CSC), are considered the most predictive models for translational oncology. Large PDX collections reflective of patient populations have been created and used extensively to test various investigational therapies, including population-trials as surrogate subjects in vivo . PDOs are recognized as in vitro surrogates for patients amenable for high-throughput screening (HTS). We have built a biobank of carcinoma PDX-derived organoids (PDXOs) by converting an existing PDX library and confirmed high degree of similarities between PDXOs and parental PDXs in genomics, histopathology and pharmacology, suggesting “biological equivalence or interchangeability” between the two. Here we demonstrate the applications of PDXO biobank for HTS “matrix” screening for both lead compounds and indications, immune cell co-cultures for immune-therapies and engineering enables in vitro/in vivo imaging. This large biobank of >550 matched pairs of PDXs/PDXOs across different cancers could become powerful tools for the future cancer drug discovery.
Audience Academic
Author Xu, Xiaoxi
Guo, Sheng
Clevers, Hans
Zhou, Jun
Wang, Jingjing
Wang, Haojie
Chen, Xiaobo
Bao, Zhengzheng
Wang, Fei
Zheng, Meiling
An, Xiaoyu
Vries, Robert G. J.
Kumari, Rajendra
Tu, Xiaolong
Shang, Limei
Zhang, Likun
Dong, Xin
Ouyang, Xuesong
Mao, Binchen
Zhang, Rui
Tian, Xiaoli
Li, Qi-Xiang
Chen, Jing
Yan, Xuefei
AuthorAffiliation 3 Crown Bioscience Inc., Taicang City, Jiangsu, China
6 Hubrecht Organoid Technology (HUB), Utrecht, The Netherlands
7 Oncode Institute, Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center, Utrecht, The Netherlands
5 Suzhou NeoLogics Bioscience Co, LTD, Suzhou, China
Bauer Research Foundation, UNITED STATES
1 Crown Bioscience Inc., Beijing, China
4 Shanghai Yihao Biological Technology, Xuhui District, Shanghai, China
2 Crown Bioscience Inc., San Diego, California, United States of America
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/36602988$$D View this record in MEDLINE/PubMed
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Copyright Copyright: © 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
COPYRIGHT 2023 Public Library of Science
2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
2023 Xu et al 2023 Xu et al
Copyright_xml – notice: Copyright: © 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
– notice: COPYRIGHT 2023 Public Library of Science
– notice: 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.
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License Copyright: © 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Competing Interests: X.X., J.Z., J.C., M.Z., J.W., X.T., X.A., X.C., L.Z., Z.B., L.S., F.W., X.Y, R.Z., S.G., B.M., X.O., R.K. and Q-X.L. are employees of Crown Bioscience, Inc; H.C. is inventor on several patents related to organoid technology; R.G.J.V. is an employee of HUB; X.T. is a full-time employee of Shanghai Yihao Biological Technology; H.W. and X.D are full-time employees of Suzhou Neologics Bioscience Co, LTD.
ORCID 0000-0001-8961-1681
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Snippet Patient-derived tumor xenograft (PDX)/organoid (PDO), driven by cancer stem cells (CSC), are considered the most predictive models for translational oncology....
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SubjectTerms Animals
Antimitotic agents
Antineoplastic agents
Antineoplastic Agents - pharmacology
Biobanks
Biological Specimen Banks
Biological specimens
Cancer
Clinical trials
Collections and collecting
Colorectal cancer
Disease Models, Animal
Drug dosages
Gastric cancer
Genomics
Heterografts
High-throughput screening
Histopathology
Humans
Immune system
In vivo methods and tests
Laboratory animals
Lead compounds
Liver cancer
Medicine and Health Sciences
Neoplasms - drug therapy
Neoplasms - genetics
Neoplasms - pathology
Oncology, Experimental
Organoids
Pharmacology
Prediction models
R&D
Research & development
Research and Analysis Methods
Stem cells
Tissue banks
Tumors
Xenograft Model Antitumor Assays
Xenografts
Xenotransplantation
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Title A living biobank of matched pairs of patient-derived xenografts and organoids for cancer pharmacology
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http://dx.doi.org/10.1371/journal.pone.0279821
Volume 18
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