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

Xiaoxi Xu; Rajendra Kumari; Jun Zhou; Jing Chen; Binchen Mao; Jingjing Wang; Meiling Zheng; Xiaolong Tu; Xiaoyu An; Xiaobo Chen; Likun Zhang; Xiaoli Tian; Haojie Wang; Xin Dong; Zhengzheng Bao; Sheng Guo; Xuesong Ouyang; Limei Shang; Fei Wang; Xuefei Yan; Rui Zhang; Robert G J Vries; Hans Clevers; Qi-Xiang Li

doi:10.1371/journal.pone.0279821

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

Xiaoxi Xu, Rajendra Kumari, Jun Zhou, Jing Chen, Binchen Mao, Jingjing Wang, Meiling Zheng, Xiaolong Tu, Xiaoyu An, Xiaobo Chen, Likun Zhang, Xiaoli Tian, Haojie Wang, Xin Dong, Zhengzheng Bao, Sheng Guo, Xuesong Ouyang, Limei Shang, Fei Wang, Xuefei YanRui Zhang, Robert G J Vries, Hans Clevers, Qi-Xiang Li

Hubrecht Institute

Research output: Contribution to journal/periodical › Article › Scientific › peer-review

5 Citations (Scopus)

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.

Original language	English
Pages (from-to)	e0279821
Journal	PLoS ONE
Volume	18
Issue number	1
DOIs	https://doi.org/10.1371/journal.pone.0279821
Publication status	Published - 2023

Keywords

Animals
Humans
Biological Specimen Banks
Heterografts
Neoplasms/drug therapy
Antineoplastic Agents/pharmacology
Disease Models, Animal
Organoids
Xenograft Model Antitumor Assays

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Xu, X., Kumari, R., Zhou, J., Chen, J., Mao, B., Wang, J., Zheng, M., Tu, X., An, X., Chen, X., Zhang, L., Tian, X., Wang, H., Dong, X., Bao, Z., Guo, S., Ouyang, X., Shang, L., Wang, F., ... Li, Q.-X. (2023). A living biobank of matched pairs of patient-derived xenografts and organoids for cancer pharmacology. PLoS ONE, 18(1), e0279821. https://doi.org/10.1371/journal.pone.0279821

@article{b220a9ad86634799a25d02bdaf0517f6,

title = "A living biobank of matched pairs of patient-derived xenografts and organoids for cancer pharmacology",

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.",

keywords = "Animals, Humans, Biological Specimen Banks, Heterografts, Neoplasms/drug therapy, Antineoplastic Agents/pharmacology, Disease Models, Animal, Organoids, Xenograft Model Antitumor Assays",

author = "Xiaoxi Xu and Rajendra Kumari and Jun Zhou and Jing Chen and Binchen Mao and Jingjing Wang and Meiling Zheng and Xiaolong Tu and Xiaoyu An and Xiaobo Chen and Likun Zhang and Xiaoli Tian and Haojie Wang and Xin Dong and Zhengzheng Bao and Sheng Guo and Xuesong Ouyang and Limei Shang and Fei Wang and Xuefei Yan and Rui Zhang and Vries, {Robert G J} and Hans Clevers and Qi-Xiang Li",

note = "Copyright: {\textcopyright} 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.",

year = "2023",

doi = "10.1371/journal.pone.0279821",

language = "English",

volume = "18",

pages = "e0279821",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "1",

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Xu, X, Kumari, R, Zhou, J, Chen, J, Mao, B, Wang, J, Zheng, M, Tu, X, An, X, Chen, X, Zhang, L, Tian, X, Wang, H, Dong, X, Bao, Z, Guo, S, Ouyang, X, Shang, L, Wang, F, Yan, X, Zhang, R, Vries, RGJ, Clevers, H & Li, Q-X 2023, 'A living biobank of matched pairs of patient-derived xenografts and organoids for cancer pharmacology', PLoS ONE, vol. 18, no. 1, pp. e0279821. https://doi.org/10.1371/journal.pone.0279821

TY - JOUR

T1 - A living biobank of matched pairs of patient-derived xenografts and organoids for cancer pharmacology

AU - Xu, Xiaoxi

AU - Kumari, Rajendra

AU - Zhou, Jun

AU - Chen, Jing

AU - Mao, Binchen

AU - Wang, Jingjing

AU - Zheng, Meiling

AU - Tu, Xiaolong

AU - An, Xiaoyu

AU - Chen, Xiaobo

AU - Zhang, Likun

AU - Tian, Xiaoli

AU - Wang, Haojie

AU - Dong, Xin

AU - Bao, Zhengzheng

AU - Guo, Sheng

AU - Ouyang, Xuesong

AU - Shang, Limei

AU - Wang, Fei

AU - Yan, Xuefei

AU - Zhang, Rui

AU - Vries, Robert G J

AU - Clevers, Hans

AU - Li, Qi-Xiang

N1 - 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.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Animals

KW - Humans

KW - Biological Specimen Banks

KW - Heterografts

KW - Neoplasms/drug therapy

KW - Antineoplastic Agents/pharmacology

KW - Disease Models, Animal

KW - Organoids

KW - Xenograft Model Antitumor Assays

U2 - 10.1371/journal.pone.0279821

DO - 10.1371/journal.pone.0279821

M3 - Article

C2 - 36602988

SN - 1932-6203

VL - 18

SP - e0279821

JO - PLoS ONE

JF - PLoS ONE

IS - 1

ER -

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

Abstract

Keywords

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