ArticleNature medicine2017
Long noncoding RNA EGFR-AS1 mediates epidermal growth factor receptor addiction and modulates treatment response in squamous cell carcinoma.
Article in Nature medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 112 papers, 2 of them syntheses that pooled it.
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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
112 citing papers in PubMed, 2 syntheses or guidelines pooled it, 169 citations in OpenAlex.
- Pooled it
- Predictive Value of EGFR-PI3K-AKT-mTOR-Pathway Inhibitor Biomarkers for Head and Neck Squamous Cell Carcinoma: A Systematic Review.Molecular diagnosis & therapy · 2021Pooled it
- AWTI-Net Enables Accurate and Interpretable Functional Assessment of Disease-Associated LncRNA Mutations.Interdisciplinary sciences, computational life sciences · 2026Article
- Pivotal role of long non-coding RNA in the development of new therapeutic approaches for plural mesothelioma.Discover oncology · 2026Review
- Review
- Characteristics of Patients with Non-Small Cell Lung Cancer and Epidermal Growth Factor Receptor Exon 20 Q787Q Mutation.Annals of surgical oncology · 2025Article
- lncRNA ZNF667‑AS1 inhibits ovarian cancer progression by interacting with the TNF signaling pathway.Experimental and therapeutic medicine · 2025Article
- CAN-Scan: A multi-omic phenotype-driven precision oncology platform identifies prognostic biomarkers of therapy response for colorectal cancer.Cell reports. Medicine · 2025Article
- LINC00870 promotes imatinib resistance in gastrointestinal stromal tumor via inhibiting PIGR glycosylation modifications.Heliyon · 2025Article
- Breakage fusion bridge cycles drive high oncogene number with moderate intratumoural heterogeneity.Nature communications · 2025Article
- Single nucleotide polymorphism and promoter methylation analysis of protein tyrosine phosphatase 1B in patients with myeloproliferative neoplasms.Translational cancer research · 2025Article
- A Comparative Study on Copy Number Variation in Subtypes of Breast Phyllodes Tumors.Breast cancer : basic and clinical research · 2025Article
- Construction of a Prognostic Model for Cervical Cancer Related to lncRNA Based on Differential Co-expression Network and Functional Study of Key Gene EGFR-AS1.Journal of Cancer · 2025Article
- Prognostic alternative mRNA splicing in lung adenocarcinoma.Frontiers in oncology · 2025Article
- Competing endogenous RNAs network dysregulation in oral cancer: a multifaceted perspective on crosstalk and competition.Cancer cell international · 2024Review
- Clinical role of the long non‑coding RNA, EGFR‑AS1, in patients with cancer: A systematic review and meta‑analysis.Oncology letters · 2024Article
- Identification of m6A/m5C-related lncRNA signature for prediction of prognosis and immunotherapy efficacy in esophageal squamous cell carcinoma.Scientific reports · 2024Article
- Hypoxia-Derived Exosomes Promote Lung Adenocarcinoma by Regulating HS3ST1-GPC4-Mediated Glycolysis.Cancers · 2024Article
- LncRNA LINC01123 promotes malignancy of ovarian cancer by targeting hsa-miR-516b-5p/VEGFA.Genes & genomics · 2024Article
- Super enhancer loci of EGFR regulate EGFR variant 8 through enhancer RNA and strongly associate with survival in HNSCCs.Molecular genetics and genomics : MGG · 2024Article
52 more citing papers are in PubMed but not listed here.
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Authors and funding
20 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeting EGFR is a validated approach in the treatment of squamous-cell cancers (SCCs), although there are no established biomarkers for predicting response. We have identified a synonymous mutation in EGFR, c.2361G>A (encoding p.Gln787Gln), in two patients with head and neck SCC (HNSCC) who were exceptional responders to gefitinib, and we showed in patient-derived cultures that the A/A genotype was associated with greater sensitivity to tyrosine kinase inhibitors (TKIs) as compared to the G/A and G/G genotypes. Remarkably, single-copy G>A nucleotide editing in isogenic models conferred a 70-fold increase in sensitivity due to decreased stability of the EGFR-AS1 long noncoding RNA (lncRNA). In the appropriate context, sensitivity could be recapitulated through EGFR-AS1 knockdown in vitro and in vivo, whereas overexpression was sufficient to induce resistance to TKIs. Reduced EGFR-AS1 levels shifted splicing toward EGFR isoform D, leading to ligand-mediated pathway activation. In co-clinical trials involving patients and patient-derived xenograft (PDX) models, tumor shrinkage was most pronounced in the context of the A/A genotype for EGFR-Q787Q, low expression of EGFR-AS1 and high expression of EGFR isoform D. Our study reveals how a 'silent' mutation influences the levels of a lncRNA, resulting in noncanonical EGFR addiction, and delineates a new predictive biomarker suite for response to EGFR TKIs.
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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.