ArticleCancer research2014
AXL mediates resistance to cetuximab therapy.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02424617 (A Multi-Center Open-Label Phase 1/2 Study of BGB324 in Combination With Erlotinib in Patients With Stage IIIb or Stage IV Non-Small Cell Lung Cancer), which is not on this map. Cited by 128 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
A Multi-Center Open-Label Phase 1/2 Study of BGB324 in Combination With Erlotinib in Patients With Stage IIIb or Stage IV Non-Small Cell Lung Cancer
Who cites it
128 citing papers in PubMed, 1 synthesis or guideline pooled it, 193 citations in OpenAlex.
- 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
- AXL at the nexus of therapeutic resistance, tumor vascularization, and immune evasion in cancer.iScience · 2026Review
- Window-of-Opportunity Study Utilizing Preoperative Cetuximab in Patients with Head and Neck Cancer.Cancer research communications · 2026Article
- Digital Twins for Targeted Therapy in Head and Neck Cancer: From Molecular Stratification to Resistance-Aware Combination Strategies.Current oncology (Toronto, Ont.) · 2026Review
- Single-Cell RNA-Sequencing Reveals Tumor Microenvironment Composition and Prior Therapy Modulate Response to Axl Inhibition.Cellular and molecular bioengineering · 2026Article
- Inhibition of autophagy increases head and neck cancer sensitivity to cetuximab and radiation therapy.Scientific reports · 2026Article
- The SPA17-AXL axis drives melanoma aggressiveness and SPA17-targeting vaccination exhibits antitumor efficacy.Frontiers in immunology · 2026Article
- Targeting AXL can effectively overcome c-Met-induced therapeutic resistance in renal cancer and promote tumor cell death through increased oxidative stress.Cancer letters · 2025Article
- Review
- Navigating TAM receptor dynamics in tumour immunotherapy.Cancer immunology, immunotherapy : CII · 2025Review
- Axl Regulation of NK Cell Activity Creates an Immunosuppressive Tumor Immune Microenvironment in Head and Neck Cancer.Cancers · 2025Article
- AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025Review
- Axl inhibitor-mediated reprogramming of the myeloid compartment of theFrontiers in immunology · 2025Article
- From Bench to Bedside: A Team's Approach to Multidisciplinary Strategies to Combat Therapeutic Resistance in Head and Neck Squamous Cell Carcinoma.Journal of clinical medicine · 2024Review
- The transcription factors NR5A1 and JUNB cooperate to activate the Axl promoter in mouse Sertoli cell lines.Molecular biology reports · 2024Article
- Mechanisms of resistance to tyrosine kinase inhibitor-targeted therapy and overcoming strategies.MedComm · 2024Review
- A phase 1 study of concurrent cabozantinib and cetuximab in recurrent or metastatic head and neck squamous cell cancer.Oral oncology · 2024Article
- Epidermal Growth Factor Receptor Targeting in Colorectal Carcinoma: Antibodies and Patient-Derived Organoids as a Smart Model to Study Therapy Resistance.International journal of molecular sciences · 2024Review
- Inhibition of the AURKA/YAP1 axis is a promising therapeutic option for overcoming cetuximab resistance in colorectal cancer stem cells.British journal of cancer · 2024Article
- Development of Resistance to Type II JAK2 Inhibitors in MPN Depends on AXL Kinase and Is Targetable.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
The EGFR antibody cetuximab is used to treat numerous cancers, but intrinsic and acquired resistance to this agent is a common clinical outcome. In this study, we show that overexpression of the oncogenic receptor tyrosine kinase AXL is sufficient to mediate acquired resistance to cetuximab in models of non-small cell lung cancer (NSCLC) and head and neck squamous cell carcinoma (HNSCC), where AXL was overexpressed, activated, and tightly associated with EGFR expression in cells resistant to cetuximab (Ctx(R) cells). Using RNAi methods and novel AXL-targeting agents, we found that AXL activation stimulated cell proliferation, EGFR activation, and MAPK signaling in Ctx(R) cells. Notably, EGFR directly regulated the expression of AXL mRNA through MAPK signaling and the transcription factor c-Jun in Ctx(R) cells, creating a positive feedback loop that maintained EGFR activation by AXL. Cetuximab-sensitive parental cells were rendered resistant to cetuximab by stable overexpression of AXL or stimulation with EGFR ligands, the latter of which increased AXL activity and association with the EGFR. In tumor xenograft models, the development of resistance following prolonged treatment with cetuximab was associated with AXL hyperactivation and EGFR association. Furthermore, in an examination of patient-derived xenografts established from surgically resected HNSCCs, AXL was overexpressed and activated in tumors that displayed intrinsic resistance to cetuximab. Collectively, our results identify AXL as a key mediator of cetuximab resistance, providing a rationale for clinical evaluation of AXL-targeting drugs to treat cetuximab-resistant cancers. Cancer Res; 74(18); 5152-64. ©2014 AACR.
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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.