Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Resolving drug effects in patient-derived cancer cells links organoid responses to genome alterations

Julia Neugebauer, Franziska M. Zickgraf, Jeongbin Park, Steve Wagner, Xiaoqi Jiang, Katharina Jechow, Kortine Kleinheinz, Umut H. Toprak, Marc A. Schneider, Michael Meister, Saskia Spaich, Marc Sütterlin, Matthias Schlesner, Andreas Trumpp, Martin Sprick, Roland Eils, Christian Conrad
doi: https://doi.org/10.1101/124446
Julia Neugebauer
1Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
2Center for Quantitative Analysis of Molecular and Cellular Biosystems (BioQuant), University of Heidelberg, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Franziska M. Zickgraf
3Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) gGmbH, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
4Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jeongbin Park
1Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Steve Wagner
3Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) gGmbH, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
4Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiaoqi Jiang
5Division of Biostatistics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 581, 69120 Heidelberg, Germany.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katharina Jechow
1Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
2Center for Quantitative Analysis of Molecular and Cellular Biosystems (BioQuant), University of Heidelberg, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kortine Kleinheinz
1Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Umut H. Toprak
1Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marc A. Schneider
6Thoraxklinik at Heidelberg University Hospital, Member of the German Center for Lung Research (DZL), Röntgenstr. 1, 69126 Heidelberg, Germany.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael Meister
6Thoraxklinik at Heidelberg University Hospital, Member of the German Center for Lung Research (DZL), Röntgenstr. 1, 69126 Heidelberg, Germany.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Saskia Spaich
7Department of Gynaecology and Obstetrics, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marc Sütterlin
7Department of Gynaecology and Obstetrics, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthias Schlesner
1Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andreas Trumpp
3Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) gGmbH, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
4Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
8German Cancer Consortium, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Martin Sprick
3Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM) gGmbH, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
4Division of Stem Cells and Cancer, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roland Eils
1Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
2Center for Quantitative Analysis of Molecular and Cellular Biosystems (BioQuant), University of Heidelberg, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany.
9Department for Bioinformatics and Functional Genomics, Institute for Pharmacy and Molecular Biotechnology (IPMB) and BioQuant, Heidelberg University, Heidelberg, Germany.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: r.eils@dkfz.de c.conrad@dkfz.de
Christian Conrad
1Division of Theoretical Bioinformatics, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
2Center for Quantitative Analysis of Molecular and Cellular Biosystems (BioQuant), University of Heidelberg, Im Neuenheimer Feld 267, 69120 Heidelberg, Germany.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: r.eils@dkfz.de c.conrad@dkfz.de
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

Cancer drug screening in patient-derived cells holds great promise for personalized oncology and drug discovery but lacks standardization. Whether cells are cultured as conventional monolayer or advanced organoid cultures influences drug effects and thereby drug selection and clinical success. To precisely compare drug profiles in differently cultured primary cells, we developed DeathPro, an automated microscopy-based assay to resolve drug-induced cell death and proliferation inhibition. Using DeathPro, we screened cells from ovarian cancer patients in monolayer or organoid culture with clinically relevant drugs. Drug-induced growth arrest and efficacy of cytostatic drugs differed between the two culture systems. Interestingly, drug effects in organoids were more diverse and had lower therapeutic potential. Genomic analysis revealed novel links between drug sensitivity and DNA repair deficiency in organoids that were undetectable in monolayers. Thus, our results highlight the dependency of cytostatic drugs and pharmacogenomic associations on culture systems, and guide culture selection for drug tests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted April 06, 2017.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Resolving drug effects in patient-derived cancer cells links organoid responses to genome alterations
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Resolving drug effects in patient-derived cancer cells links organoid responses to genome alterations
Julia Neugebauer, Franziska M. Zickgraf, Jeongbin Park, Steve Wagner, Xiaoqi Jiang, Katharina Jechow, Kortine Kleinheinz, Umut H. Toprak, Marc A. Schneider, Michael Meister, Saskia Spaich, Marc Sütterlin, Matthias Schlesner, Andreas Trumpp, Martin Sprick, Roland Eils, Christian Conrad
bioRxiv 124446; doi: https://doi.org/10.1101/124446
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Resolving drug effects in patient-derived cancer cells links organoid responses to genome alterations
Julia Neugebauer, Franziska M. Zickgraf, Jeongbin Park, Steve Wagner, Xiaoqi Jiang, Katharina Jechow, Kortine Kleinheinz, Umut H. Toprak, Marc A. Schneider, Michael Meister, Saskia Spaich, Marc Sütterlin, Matthias Schlesner, Andreas Trumpp, Martin Sprick, Roland Eils, Christian Conrad
bioRxiv 124446; doi: https://doi.org/10.1101/124446

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Cancer Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4684)
  • Biochemistry (10361)
  • Bioengineering (7682)
  • Bioinformatics (26340)
  • Biophysics (13534)
  • Cancer Biology (10692)
  • Cell Biology (15445)
  • Clinical Trials (138)
  • Developmental Biology (8501)
  • Ecology (12824)
  • Epidemiology (2067)
  • Evolutionary Biology (16867)
  • Genetics (11401)
  • Genomics (15483)
  • Immunology (10619)
  • Microbiology (25224)
  • Molecular Biology (10225)
  • Neuroscience (54480)
  • Paleontology (402)
  • Pathology (1669)
  • Pharmacology and Toxicology (2897)
  • Physiology (4345)
  • Plant Biology (9252)
  • Scientific Communication and Education (1586)
  • Synthetic Biology (2558)
  • Systems Biology (6781)
  • Zoology (1466)