Model-based analysis of response and resistance factors of cetuximab treatment in gastric cancer cell lines
Raimundez E, Keller S, Zwingenberger G, Ebert K, Hug S, Theis FJ, Maier D, Luber B, Hasenauer J (2020)
Publication Type: Journal article
Publication year: 2020
Journal
Book Volume: 16
Article Number: e1007147
Journal Issue: 3
DOI: 10.1371/journal.pcbi.1007147
Abstract
Targeted cancer therapies are powerful alternatives to chemotherapies or can be used complementary to these. Yet, the response to targeted treatments depends on a variety of factors, including mutations and expression levels, and therefore their outcome is difficult to predict. Here, we develop a mechanistic model of gastric cancer to study response and resistance factors for cetuximab treatment. The model captures the EGFR, ERK and AKT signaling pathways in two gastric cancer cell lines with different mutation patterns. We train the model using a comprehensive selection of time and dose response measurements, and provide an assessment of parameter and prediction uncertainties. We demonstrate that the proposed model facilitates the identification of causal differences between the cell lines. Furthermore, our study shows that the model provides predictions for the responses to different perturbations, such as knockdown and knockout experiments. Among other results, the model predicted the effect of MET mutations on cetuximab sensitivity. These predictive capabilities render the model a basis for the assessment of gastric cancer signaling and possibly for the development and discovery of predictive biomarkers.
Involved external institutions
Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich
Germany (DE)
Technische Universität München (TUM)
Germany (DE)
Biomax Informatics AG
Germany (DE)
Germany (DE)
Technische Universität München (TUM)
Germany (DE)
Biomax Informatics AG
Germany (DE)
How to cite
APA:
Raimundez, E., Keller, S., Zwingenberger, G., Ebert, K., Hug, S., Theis, F.J.,... Hasenauer, J. (2020). Model-based analysis of response and resistance factors of cetuximab treatment in gastric cancer cell lines. PLoS Computational Biology, 16(3). https://doi.org/10.1371/journal.pcbi.1007147
MLA:
Raimundez, Elba, et al. "Model-based analysis of response and resistance factors of cetuximab treatment in gastric cancer cell lines." PLoS Computational Biology 16.3 (2020).
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