ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Targeting Stat3 abrogates EGFR inhibitor resistance in cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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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
85 citing papers in PubMed, 159 citations in OpenAlex.
- Randomized, Double-Blind, Phase II Study of Ruxolitinib or Placebo in Combination With Capecitabine in Patients With Metastatic Pancreatic Cancer for Whom Therapy With Gemcitabine Has Failed.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2015Trial
- ABTB1 modulates EGFR signaling and confers icotinib sensitivity in lung adenocarcinoma.Respiratory research · 2026Article
- IL-6R blockade with tocilizumab disrupts pericyte- and tumor cell-driven IL-6/STAT3 signaling, enhancing docetaxel efficacy in ER+ breast cancer.bioRxiv : the preprint server for biology · 2026Article
- Protacs in oral cancer: degrading oncogenic drivers for next-generation therapy.Frontiers in oral health · 2026Review
- Current and Emerging Protein Biomarkers for the Diagnosis and Prognosis of Head and Neck Cancer.Genes · 2025Review
- Safety and efficacy of a STAT3-targeted cyclic oligonucleotide: From murine models to a phase 1 clinical trial in pet cats with oral cancer.Cancer cell · 2025Article
- LCP1 upregulation via EGFR signaling promotes oral cancer progression through the JAK2/STAT3/IL-1β axis.Cancer cell international · 2025Article
- Repurposing Amiodarone for Bladder Cancer Treatment.Cancer research communications · 2025Article
- Article
- HOXB8 mediates resistance to cetuximab in colorectal cancer cells through activation of the STAT3 pathway.Discover oncology · 2024Article
- pSTAT3 transactivates EGFR in maintaining EGFR protein homeostasis and EGFR-TKI resistance.Acta biochimica et biophysica Sinica · 2024Article
- STAT3 Protein-Protein Interaction Analysis Finds P300 as a Regulator of STAT3 and Histone 3 Lysine 27 Acetylation in Pericytes.Biomedicines · 2024Article
- Crosstalk between CAFs and tumour cells in head and neck cancer.Cell death discovery · 2024Review
- Interleukin-6 serves as a critical factor in various cancer progression and therapy.Medical oncology (Northwood, London, England) · 2024Review
- Overcoming Resistance to Standard-of-Care Therapies for Head and Neck Squamous Cell Carcinomas.Cells · 2024Review
- Targeting CD24 as a novel immunotherapy for solid cancers.Cell communication and signaling : CCS · 2023Review
- EGFR TKI resistance in lung cancer cells using RNA sequencing and analytical bioinformatics tools.Journal of biomolecular structure & dynamics · 2023Article
- The Role of the JAK/STAT Signaling Pathway in the Pathogenesis of Alzheimer's Disease: New Potential Treatment Target.International journal of molecular sciences · 2023Review
- Transcriptomic and Proteomic Profiles for Elucidating Cisplatin Resistance in Head-and-Neck Squamous Cell Carcinoma.Cancers · 2022Article
- The multifaceted role of STAT3 pathway and its implication as a potential therapeutic target in oral cancer.Archives of pharmacal research · 2022Review
25 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
purposeEGF receptor (EGFR) is upregulated in most epithelial cancers where signaling through EGFR contributes to cancer cell proliferation and survival. The limited clinical efficacy of EGFR inhibitors suggests that identification of resistance mechanisms may identify new pathways for therapeutic targeting. STAT3 is upregulated in many cancers and activated via both EGFR-dependent and -independent pathways. In the present study, we tested the consequences of STAT3 inhibition in EGFR inhibitor-resistant head and neck squamous cell carcinoma (HNSCC) and bladder cancer models to determine whether STAT3 blockade can enhance responses to EGFR targeting. EXPERIMENTAL
designpSTAT3 expression was assessed in human HNSCC tumors that recurred following cetuximab treatment. Cetuximab-sensitive and -resistant cell lines were treated with a STAT3 decoy to determine EC(50) concentrations and the effects on STAT3 target gene expression by Western blotting. In vivo assays included evaluation of antitumor efficacy of STAT3 decoy in cetuximab-sensitive and -resistant models followed by immunoblotting for STAT3 target protein expression.
resultsTargeting STAT3 with a STAT3 decoy reduced cellular viability and the expression of STAT3 target genes in EGFR inhibitor resistance models. The addition of a STAT3 inhibitor to EGFR blocking strategies significantly enhanced antitumor effects in vivo. Biopsies from HNSCC tumors that recurred following cetuximab treatment showed increased STAT3 activation compared with pretreatment biopsies.
conclusionsThese results suggest that STAT3 activation contributes to EGFR inhibitor resistance both in HNSCC and bladder cancer where concomitant targeting of STAT3 may represent an effective treatment strategy.
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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.