ArticleScience signaling2014
Systematic identification of signaling pathways with potential to confer anticancer drug resistance.
Article in Science signaling, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers, 1 of them a synthesis that pooled it.
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Who cites it
125 citing papers in PubMed, 1 synthesis or guideline pooled it, 197 citations in OpenAlex.
- Pooled it
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- Advances in high-throughput drug screening based on pharmacotranscriptomics.Journal of advanced research · 2026Review
- Pooled single-cell screen in colorectal cancer defines transcriptional modules linked to oncogenes.Molecular systems biology · 2026Article
- EGFR inhibitor-resistant lung cancers exhibit collateral sensitivity to a covalent, cysteine-independent KEAP1 oligomerizing molecular bridge.Nature communications · 2026Article
- Unlocking the Power of CXCR2 Inhibition to Overcome Gemcitabine Resistance in Pancreatic Cancer.FASEB bioAdvances · 2026Article
- Revealing miRNAs' Janus-Faced Nature: Transforming Cold Tumours into Immunotherapy Hotspots and Overcoming Chemoresistance.MicroRNA (Shariqah, United Arab Emirates) · 2026Review
- Article
- Combination of HDAC inhibitor and PI3K inhibitor suppresses autophagy and induces apoptosis via cytoplasmic IκBα stabilization in p53-mutant diffuse large B-cell lymphoma.Cell death discovery · 2025Article
- Initiation of meiosis from human iPSCs under defined conditions through identification of regulatory factors.Science advances · 2025Article
- Ref-1 redox activity modulates canonical Wnt signaling in endothelial cells.Redox biology · 2025Article
- GLI2 Facilitates Tumor Immune Evasion and Immunotherapeutic Resistance by Coordinating WNT and Prostaglandin Signaling.Cancer research · 2025Article
- Oncogenic HRAS Induces Metformin Resistance in Head and Neck Cancer by Promoting Glycolytic Metabolism.Cancer prevention research (Philadelphia, Pa.) · 2024Article
- γ-Glutamylcyclotransferase is transcriptionally regulated by c-Jun and controls proliferation of glioblastoma stem cells through Notch1 levels.Cancer gene therapy · 2024Article
- Targeting a lineage-specific PI3Kɣ-Akt signaling module in acute myeloid leukemia using a heterobifunctional degrader molecule.Nature cancer · 2024Article
- Defining the KRAS- and ERK-dependent transcriptome in KRAS-mutant cancers.Science (New York, N.Y.) · 2024Article
- Induction of Meiosis from Human Pluripotent Stem Cells.bioRxiv : the preprint server for biology · 2024Article
- Semaphorin Receptors Antagonize Wnt Signaling Through Beta-Catenin Degradation.bioRxiv : the preprint server for biology · 2024Article
- NRN1 interacts with Notch to increase oncogenic STAT3 signaling in melanoma.Cell communication and signaling : CCS · 2024Article
- Defining the Functional Influence of Endothelial Cell-Expressed Oncogenic Activating Mutations on Vascular Morphogenesis and Capillary Assembly.The American journal of pathology · 2024Article
65 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 1 country.
Funding
Abstract
Cancer cells can activate diverse signaling pathways to evade the cytotoxic action of drugs. We created and screened a library of barcoded pathway-activating mutant complementary DNAs to identify those that enhanced the survival of cancer cells in the presence of 13 clinically relevant, targeted therapies. We found that activation of the RAS-MAPK (mitogen-activated protein kinase), Notch1, PI3K (phosphoinositide 3-kinase)-mTOR (mechanistic target of rapamycin), and ER (estrogen receptor) signaling pathways often conferred resistance to this selection of drugs. Activation of the Notch1 pathway promoted acquired resistance to tamoxifen (an ER-targeted therapy) in serially passaged breast cancer xenografts in mice, and treating mice with a γ-secretase inhibitor to inhibit Notch signaling restored tamoxifen sensitivity. Markers of Notch1 activity in tumor tissue correlated with resistance to tamoxifen in breast cancer patients. Similarly, activation of Notch1 signaling promoted acquired resistance to MAPK inhibitors in BRAF(V600E) melanoma cells in culture, and the abundance of Notch1 pathway markers was increased in tumors from a subset of melanoma patients. Thus, Notch1 signaling may be a therapeutic target in some drug-resistant breast cancers and melanomas. Additionally, multiple resistance pathways were activated in melanoma cell lines with intrinsic resistance to MAPK inhibitors, and simultaneous inhibition of these pathways synergistically induced drug sensitivity. These data illustrate the potential for systematic identification of the signaling pathways controlling drug resistance that could inform clinical strategies and drug development for multiple types of cancer. This approach may also be used to advance clinical options in other disease contexts.
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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.