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Cited by 43HER2/EGFR in Cancer ResearchCancer Cells and Metastasis3D Printing in Biomedical Research

Organotypic three-dimensional cancer cell cultures mirror drug responses in vivo: lessons learned from the inhibition of EGFR signaling

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Jacobi, Nico, Seeboeck, Rita, Hofmann, Elisabeth, Schweiger, Helmut, Smolinska, Veronika, Mohr, Thomas, Boyer, Alexandra, Sommergruber, Wolfgang +6 more·2017·Oncotarget
DOI 10.18632/oncotarget.22475PMC PMC5746077
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Abstract

// Nico Jacobi 1 , Rita Seeboeck 2 , Elisabeth Hofmann 2 , Helmut Schweiger 1 , Veronika Smolinska 1 , Thomas Mohr 3 , Alexandra Boyer 1 , Wolfgang Sommergruber 4 , Peter Lechner 5 , Corina Pichler-Huebschmann 5 , Kamil Önder 6, 7 , Harald Hundsberger 2 , Christoph Wiesner 2 and Andreas Eger 1, 2 1 IMC University of Applied Sciences Krems, Department Life Sciences, Research Institute for Applied Bioanalytics and Drug Development, A-3500 Krems, Austria 2 IMC University of Applied Sciences Krems, Department Life Sciences, Institute of Medical and Pharmaceutical Biotechnology, A-3500 Krems, Austria 3 Medical University of Vienna, Institute for Cancer Research, A-1090 Vienna, Austria 4 Boehringer Ingelheim, RCV GmbH and Co KG, A-1121 Vienna, Austria 5 University Clinic Tulln, Department Surgery, A-3430 Tulln, Austria 6 Research Program for Rational Drug Design in Dermatology and Rheumatology, Department of Dermatology, Paracelsus Medical University of Salzburg, A-5020 Salzburg, Austria 7 ProComCure Biotech, A-5081 Anif, Austria Correspondence to: Andreas Eger, email: andreas.eger@fh-krems.ac.at Keywords: drug discovery; 3D models; ERBB signaling; targeted drugs; oncogene addiction Received: August 25, 2017 Accepted: October 27, 2017 Published: November 17, 2017 ABSTRACT Complex three-dimensional (3D) in vitro models that recapitulate human tumor biology are essential to understand the pathophysiology of the disease and to aid in the discovery of novel anti-cancer therapies. 3D organotypic cultures exhibit intercellular communication, nutrient and oxygen gradients, and cell polarity that is lacking in two-dimensional (2D) monolayer cultures. In the present study, we demonstrate that 2D and 3D cancer models exhibit different drug sensitivities towards both targeted inhibitors of EGFR signaling and broad acting cytotoxic agents. Changes in the kinase activities of ErbB family members and differential expression of apoptosis- and survival-associated genes before and after drug treatment may account for the differential drug sensitivities. Importantly, EGFR oncoprotein addiction was evident only in the 3D cultures mirroring the effect of EGFR inhibition in the clinic. Furthermore, targeted drug efficacy was strongly increased when incorporating cancer-associated fibroblasts into the 3D cultures. Taken together, we provide conclusive evidence that complex 3D cultures are more predictive of the clinical outcome than their 2D counterparts. In the future, 3D cultures will be instrumental for understanding the mode of action of drugs, identifying genotype-drug response relationships and developing patient-specific and personalized cancer treatments.

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  • When cultured in 3D systems, tumor cells often exhibit altered expression of key molecular markers associated with proliferation, apoptosis, drug resistance, and differentiation compared to their 2D counterparts.

    “When cultured in 3D systems, tumor cells often exhibit altered expression of key molecular markers associated with proliferation, apoptosis, drug resistance, and differentiation, compared to their 2D counterparts [10].”

    From Modeling Tumor Microenvironment Complexity In Vitro: Spheroids as Physiologically Relevant Tumor Models and Strategies for Their Analysis (2025) · cites this paper as [10]

    The Results section, “2D and 3D cancer models exhibit differences in gene expression” (page unavailable), reports altered expression of apoptosis- and survival-associated genes in 3D versus 2D cultures. The Discussion (page unavailable) also reports changes in ErbB expression alongside lower proliferation in spheroids and different drug responses. The paper does not establish altered expression of differentiation or drug-resistance markers as the claim states; differences in drug response are not themselves evidence of altered drug-resistance-marker expression. (LLM, conf=0.86)

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Cited by

Sorted by citations

Authors
Jacobi, N., Seeboeck, R., Hofmann, E., Schweiger, H., Smolinska, V., Mohr, T., Boyer, A., Sommergruber, W., Lechner, P., Pichler-Huebschmann, C., Önder, K., Hundsberger, H., Wiesner, C., & Eger, A.
Affiliations
  • IMC University of Applied Sciences Krems (AT)
  • IMC University of Applied Sciences Krems, Department Life Sciences, Research Institute for Applied Bioanalytics and Drug Development, A-3500 Krems, Austria
  • Medical University of Vienna (AT)
  • Boehringer Ingelheim (Austria) (AT)
  • Universitätsklinikum Tulln (AT)
  • University of Salzburg (AT)
Corresponding author
Eger, Andreas
ORCID
Venue
Oncotarget
Publisher
Impact Journals, LLC
Published
2017-11-17
Volume
8
Issue
64
Pages
107423-107440
ISSN
1949-2553 (ISSN-L)
DOI
10.18632/oncotarget.22475
PMC
PMC5746077
OpenAlex
W2769445627
Cited by
43
References
12
Citations by year
2026: 2 · 2025: 3 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 9 · 2020: 9 · 2019: 6 · 2018: 1
FWCI
1.93
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Oncotarget (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Physical Sciences › Engineering › Biomedical Engineering › 3D Printing in Biomedical Research
Keywords
cancer cell models, EGFR signaling, EGFR inhibitors, drug sensitivity, ErbB family, oncogene addiction, apoptosis, cell survival genes, cytotoxic drugs, 2D vs 3D culture comparison, intercellular communication, cell polarity, targeted therapy

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