ArticleScience signaling2010
Synthetic lethal screen of an EGFR-centered network to improve targeted therapies.
Article in Science signaling, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
93 citing papers in PubMed, 1 synthesis or guideline pooled it, 142 citations in OpenAlex.
- Synthetic lethal gene pairs: Experimental approaches and predictive models.Frontiers in genetics · 2022Pooled it
- NN-01-195, a Novel Conjugate of HSP90 and AURKA Inhibitors, Effectively Targets Solid Tumors.Molecular cancer therapeutics · 2026Article
- Combination AURKA and WEE1 Inhibition Exhibits Efficacy in EGFR or Pan-ERBB Inhibitor-Resistant Head and Neck Squamous Cell Carcinoma.Cancer research communications · 2026Article
- Inferring spatial single-cell-level interactions through interpreting cell state and niche correlations learned by self-supervised graph transformer.Nature machine intelligence · 2026Article
- Functional modules predict cancer-relevant genetic interactions in mammalian cells.bioRxiv : the preprint server for biology · 2025Article
- Osteosarcoma Multi-Omics Landscape and Subtypes.Cancers · 2023Article
- Discovery of synthetic lethal interactions from large-scale pan-cancer perturbation screens.Nature communications · 2022Article
- Proteogenomic analysis of lung adenocarcinoma reveals tumor heterogeneity, survival determinants, and therapeutically relevant pathways.Cell reports. Medicine · 2022Article
- NEDD9 Restrains dsDNA Damage Response during Non-Small Cell Lung Cancer (NSCLC) Progression.Cancers · 2022Article
- Aurora kinase blockade drives de novo addiction of cervical squamous cell carcinoma to druggable EGFR signalling.Oncogene · 2022Article
- Ex vivo organotypic cultures for synergistic therapy prioritization identify patient-specific responses to combined MEK and Src inhibition in colorectal cancer.Nature cancer · 2022Article
- How to Achieve Therapeutic Response in Erlotinib-Resistant Head and Neck Squamous Cell Carcinoma? New Insights from Stable Isotope Labeling with Amino Acids in Cell Culture-Based Quantitative Tyrosine Phosphoproteomics.Omics : a journal of integrative biology · 2021Article
- Article
- Oncoprotein-specific molecular interaction maps (SigMaps) for cancer network analyses.Nature biotechnology · 2021Article
- Combined inhibition of Ref-1 and STAT3 leads to synergistic tumour inhibition in multiple cancers using 3D and in vivo tumour co-culture models.Journal of cellular and molecular medicine · 2021Article
- Bioinformatic analysis revealing mitotic spindle assembly regulated NDC80 and MAD2L1 as prognostic biomarkers in non-small cell lung cancer development.BMC medical genomics · 2020Article
- Article
- RNA interference screening methods to identify proliferation determinants and mechanisms of resistance to immune attack.Methods in enzymology · 2020Article
- Targeting positive feedback between BASP1 and EGFR as a therapeutic strategy for lung cancer progression.Theranostics · 2020Article
- Combined Aurora Kinase A (AURKA) and WEE1 Inhibition Demonstrates Synergistic Antitumor Effect in Squamous Cell Carcinoma of the Head and Neck.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
33 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
17 authors at 2 institutions in 1 country.
Funding
Abstract
Intrinsic and acquired cellular resistance factors limit the efficacy of most targeted cancer therapeutics. Synthetic lethal screens in lower eukaryotes suggest that networks of genes closely linked to therapeutic targets would be enriched for determinants of drug resistance. We developed a protein network centered on the epidermal growth factor receptor (EGFR), which is a validated cancer therapeutic target, and used small interfering RNA screening to comparatively probe this network for proteins that regulate the effectiveness of both EGFR-targeted agents and nonspecific cytotoxic agents. We identified subnetworks of proteins influencing resistance, with putative resistance determinants enriched among proteins that interacted with proteins at the core of the network. We found that clinically relevant drugs targeting proteins connected in the EGFR network, such as protein kinase C or Aurora kinase A, or the transcriptional regulator signal transducer and activator of transcription 3 (STAT3), synergized with EGFR antagonists to reduce cell viability and tumor size, suggesting the potential for a direct path to clinical exploitation. Such a focused approach can potentially improve the coherent design of combination cancer therapies.
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What OpenQuestion holds
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.