ArticleMolecular systems biology2013
Network quantification of EGFR signaling unveils potential for targeted combination therapy.
Article in Molecular systems biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
89 citing papers in PubMed, 175 citations in OpenAlex.
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- Reporter-based screening identifies RAS-RAF mutations as drivers of resistance to active-state RAS inhibitors in colorectal cancer.Science signaling · 2025Article
- Spike-in enhanced phosphoproteomics uncovers synergistic signaling responses to MEK inhibition in colon cancer cells.Nature communications · 2025Article
- Quantitative modeling of signaling in aggressive B cell lymphoma unveils conserved core network.PLoS computational biology · 2024Article
- Cell-specific models reveal conformation-specific RAF inhibitor combinations that synergistically inhibit ERK signaling in pancreatic cancer cells.Cell reports · 2024Article
- PCA-based synthetic sensitivity coefficients for chemical reaction network in cancer.Scientific reports · 2024Article
- Modeling unveils sex differences of signaling networks in mouse embryonic stem cells.Molecular systems biology · 2023Article
- Himalayan flora: targeting various molecular pathways in lung cancer.Medical oncology (Northwood, London, England) · 2023Review
- Distribution modeling quantifies collective TScience advances · 2023Article
- Critical transition and reversion of tumorigenesis.Experimental & molecular medicine · 2023Review
- Fine tuning a logical model of cancer cells to predict drug synergies: combining manual curation and automated parameterization.Frontiers in systems biology · 2023Article
- Design and selection of optimal ErbB-targeting bispecific antibodies in pancreatic cancer.Frontiers in immunology · 2023Article
- Network inference from perturbation time course data.NPJ systems biology and applications · 2022Article
- Identifying mutant-specific multi-drug combinations using comparative network reconstruction.iScience · 2022Article
- Mutations in ALK signaling pathways conferring resistance to ALK inhibitor treatment lead to collateral vulnerabilities in neuroblastoma cells.Molecular cancer · 2022Article
- Application of modular response analysis to medium- to large-size biological systems.PLoS computational biology · 2022Article
- A multiscale cell-based model of tumor growth for chemotherapy assessment and tumor-targeted therapy through a 3D computational approach.Cell proliferation · 2022Article
- Transcriptome analysis revealed the role of mTOR and MAPK signaling pathways in the white strain ofFrontiers in pharmacology · 2022Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The epidermal growth factor receptor (EGFR) signaling network is activated in most solid tumors, and small-molecule drugs targeting this network are increasingly available. However, often only specific combinations of inhibitors are effective. Therefore, the prediction of potent combinatorial treatments is a major challenge in targeted cancer therapy. In this study, we demonstrate how a model-based evaluation of signaling data can assist in finding the most suitable treatment combination. We generated a perturbation data set by monitoring the response of RAS/PI3K signaling to combined stimulations and inhibitions in a panel of colorectal cancer cell lines, which we analyzed using mathematical models. We detected that a negative feedback involving EGFR mediates strong cross talk from ERK to AKT. Consequently, when inhibiting MAPK, AKT activity is increased in an EGFR-dependent manner. Using the model, we predict that in contrast to single inhibition, combined inactivation of MEK and EGFR could inactivate both endpoints of RAS, ERK and AKT. We further could demonstrate that this combination blocked cell growth in BRAF- as well as KRAS-mutated tumor cells, which we confirmed using a xenograft model.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.