ArticleScience signaling2013
Drug synergy screen and network modeling in dedifferentiated liposarcoma identifies CDK4 and IGF1R as synergistic drug targets.
Article in Science signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
49 citing papers in PubMed, 88 citations in OpenAlex.
- Clinical utility of PDX cohorts to reveal biomarkers of intrinsic resistance and clonal architecture changes underlying acquired resistance to cetuximab in HNSCC.Signal transduction and targeted therapy · 2022Trial
- CDK4/6 inhibition induces a senescence-associated secretory phenotype via delayed NF-κB activation.Life science alliance · 2026Article
- Genetic, Epigenetic and Transcriptome Alterations in Liposarcoma for Target Therapy Selection.Cancers · 2024Review
- Computational screen for sex-specific drug effects in a cardiac fibroblast signaling network model.Scientific reports · 2023Article
- A comprehensive mechanistic model of adipocyte signaling with layers of confidence.NPJ systems biology and applications · 2023Article
- Discovery of Ruthenium(II) Metallocompound and Olaparib Synergy for Cancer Combination Therapy.Journal of medicinal chemistry · 2023Article
- Fine tuning a logical model of cancer cells to predict drug synergies: combining manual curation and automated parameterization.Frontiers in systems biology · 2023Article
- The Role of ARID1A in the Nonestrogenic Modulation of IGF-1 Signaling.Molecular cancer research : MCR · 2022Article
- Beyond targeting amplified MDM2 and CDK4 in well differentiated and dedifferentiated liposarcomas: From promise and clinical applications towards identification of progression drivers.Frontiers in oncology · 2022Review
- The Art and Science of Building a Computational Model to Understand Hemostasis.Seminars in thrombosis and hemostasis · 2021Review
- Chemical-Genetic Interactions as a Means to Characterize Drug Synergy.Methods in molecular biology (Clifton, N.J.) · 2021Review
- Drug antagonism and single-agent dominance result from differences in death kinetics.Nature chemical biology · 2020Article
- Perturbation biology links temporal protein changes to drug responses in a melanoma cell line.PLoS computational biology · 2020Article
- Direct targeting of oncogenic RAS mutants with a tumor-specific cytosol-penetrating antibody inhibits RAS mutant-driven tumor growth.Science advances · 2020Article
- A Middle-Out Modeling Strategy to Extend a Colon Cancer Logical Model Improves Drug Synergy Predictions in Epithelial-Derived Cancer Cell Lines.Frontiers in molecular biosciences · 2020Article
- Strategies to Enhance Logic Modeling-Based Cell Line-Specific Drug Synergy Prediction.Frontiers in physiology · 2020Article
- Targeted Gene Expression Profile Reveals CDK4 as Therapeutic Target for Selected Patients With Adrenocortical Carcinoma.Frontiers in endocrinology · 2020Article
- Synergistic Cytotoxicity of Renieramycin M and Doxorubicin in MCF-7 Breast Cancer Cells.Marine drugs · 2019Article
- A Combination CDK4/6 and IGF1R Inhibitor Strategy for Ewing Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Dynamic Targeting in Cancer Treatment.Frontiers in physiology · 2019Article
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Dedifferentiated liposarcoma (DDLS) is a rare but aggressive cancer with high recurrence and low response rates to targeted therapies. Increasing treatment efficacy may require combinations of targeted agents that counteract the effects of multiple abnormalities. To identify a possible multicomponent therapy, we performed a combinatorial drug screen in a DDLS-derived cell line and identified cyclin-dependent kinase 4 (CDK4) and insulin-like growth factor 1 receptor (IGF1R) as synergistic drug targets. We measured the phosphorylation of multiple proteins and cell viability in response to systematic drug combinations and derived computational models of the signaling network. These models predict that the observed synergy in reducing cell viability with CDK4 and IGF1R inhibitors depends on the activity of the AKT pathway. Experiments confirmed that combined inhibition of CDK4 and IGF1R cooperatively suppresses the activation of proteins within the AKT pathway. Consistent with these findings, synergistic reductions in cell viability were also found when combining CDK4 inhibition with inhibition of either AKT or epidermal growth factor receptor (EGFR), another receptor similar to IGF1R that activates AKT. Thus, network models derived from context-specific proteomic measurements of systematically perturbed cancer cells may reveal cancer-specific signaling mechanisms and aid in the design of effective combination therapies.
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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.