Reference : Primary and recurrent glioma patient-derived orthotopic xenografts (PDOX) represent r...
E-prints/Working papers : Already available on another site
Human health sciences : Oncology
http://hdl.handle.net/10993/43022
Primary and recurrent glioma patient-derived orthotopic xenografts (PDOX) represent relevant patient avatars for precision medicine
English
Golebiewska, Anna mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) >]
Hau, Ann-Christin [> >]
Oudin, Anais [> >]
Stieber, Daniel [> >]
Yabo, Yahaya A. [> >]
Baus, Virginie [> >]
Barthelemy, Vanessa [> >]
Klein, Eliane [> >]
Bougnaud, Sebastien [> >]
Keunen, Olivier [> >]
Wantz, May [> >]
Michelucci, Alessandro mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Neirinckx, Virginie [> >]
Muller, Arnaud [> >]
Kaoma, Tony [> >]
Nazarov, Petr V. [> >]
Azuaje, Francisco mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) >]
De Falco, Alfonso [> >]
Flies, Ben [> >]
Richart, Lorraine [> >]
Poovathingal, Suresh [> >]
Arns, Thais mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Grzyb, Kamil mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Mock, Andreas [> >]
Herold-Mende, Christel [> >]
Steino, Anne [> >]
Brown, Dennis [> >]
May, Patrick mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Miletic, Hrvoje [> >]
Malta, Tathiane M. [> >]
Noushmehr, Houtan [> >]
Kwon, Yong-Jun mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Jahn, Winnie [> >]
Klink, Barbara [> >]
Tanner, Georgette [> >]
Stead, Lucy F. [> >]
Mittelbronn, Michel mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Skupin, Alexander mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Hertel, Frank mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Bjerkvig, Rolf [> >]
Niclou, Simone mailto [University of Luxembourg > Faculty of Science, Technology and Communication (FSTC) >]
24-Apr-2020
Cold Spring Harbor Laboratory
Yes
[en] Glioma ; Glioblastoma ; Glioma recurrence ; Precision medicine ; Preclinical models ; Organoids ; Patient-derived orthotopic xenograft ; MGMT ; IDH1
[en] Patient-derived cancer models are essential tools for studying tumor biology and preclinical interventions. Here, we show that glioma patient-derived orthotopic xenografts (PDOXs) enable long-term propagation of patient tumors and represent clinically relevant patient avatars. We created a large collection of PDOXs from primary and recurrent gliomas with and without mutations in IDH1, which retained histopathological, genetic, epigenetic and transcriptomic features of patient tumors with no mouse-specific clonal evolution. Longitudinal PDOX models recapitulate the limited genetic evolution of gliomas observed in patient tumors following treatment. PDOX-derived standardized tumor organoid cultures enabled assessment of drug responses, which were validated in mice. PDOXs showed clinically relevant responses to Temozolomide and to targeted treatments such as EGFR and CDK4/6 inhibitors in (epi)genetically defined groups, according to MGMT promoter and EGFR/CDK status respectively. Dianhydrogalactitol, a bifunctional alkylating agent, showed promising potential against glioblastoma. Our study underlines the clinical relevance of glioma PDOX models for translational research and personalized treatment studies.
Luxembourg Institute of Health - LIH ; Luxembourg Centre for Systems Biomedicine (LCSB): Integrative Cell Signalling (Skupin Group) ; Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group)
Télévie-FNRS (Grants n°7.4632.17, 4615.18) ; Fondation Cancer Luxembourg (Pan-RTK Targeting) ; FNR; CORE Junior C17/BM/11664971/DEMICS ; GLIOTRAIN ITN funded by the European Union’s Horizon 2020 ; Marie Skłodowska-Curie grant agreement No 766069 ; FNR PEARL P16/BM/11192868 grant
Researchers ; Professionals
http://hdl.handle.net/10993/43022
10.1101/2020.04.24.057802
https://www.biorxiv.org/content/early/2020/04/25/2020.04.24.057802
https://www.biorxiv.org/content/10.1101/2020.04.24.057802v1
H2020 ; 766069 - GLIOTRAIN - Exploiting GLIOblastoma intractability to address European research TRAINing needs in translational brain tumour research, cancer systems medicine and integrative multi-omics

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