ArticleJournal of clinical oncology : official journal of the American Society of Clinical Oncology2023
Resistance Mechanisms to Anti-Epidermal Growth Factor Receptor Therapy in
Article in Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 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
51 citing papers in PubMed, 67 citations in OpenAlex.
- Circulating tumour DNA to guide rechallenge with cetuximab plus irinotecan in RAS/BRAF wild-type metastatic colorectal cancer: A nonrandomised clinical trial.Clinical and translational medicine · 2026Trial
- STRATEGIC-1: multiple-line, randomized, open-label GERCOR-PRODIGE-39 phase III trial in unresectable RAS/BRAF wild-type metastatic colorectal cancer.Signal transduction and targeted therapy · 2026Trial
- Ligand-activated EGFR/MAPK signaling but not PI3K, are key resistance mechanisms to EGFR-therapy in colorectal cancer.Nature communications · 2025Trial
- Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial.Nature medicine · 2025Trial
- Intermittent or Continuous Panitumumab Plus Fluorouracil, Leucovorin, and Irinotecan for First-Line Treatment ofJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Trial
- Molecular profiling of BRAF-V600E-mutant metastatic colorectal cancer in the phase 3 BEACON CRC trial.Nature medicine · 2024Trial
- A Phase II Study of Potentiation of Pembrolizumab with Binimetinib and Bevacizumab in Refractory Microsatellite-Stable Colorectal Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Prognostic impact of circulating tumoriScience · 2026Article
- Development and validation of a multivariable CT-based Delta-radiomics model for predicting efficacy to bevacizumab therapy in patients with colorectal liver metastases.Translational cancer research · 2026Article
- Cetuximab combination with cytokine induced killer cells effectively inhibit conjunctival squamous cell carcinoma in vitro.BMC immunology · 2026Article
- TP53 mutation is associated with improved disease control in patients with advanced RAS wild-type colorectal adenocarcinoma treated with cetuximab and pembrolizumab.International journal of cancer · 2026Article
- Liquid Biopsy in Colorectal Cancer: Future Perspectives Through the Lens of Artificial Intelligence-A Comprehensive Review of Novel Literature.International journal of molecular sciences · 2026Review
- Profiling KRAS mutations in whole blood by error-corrected maximum depth sequencing.NPJ precision oncology · 2026Article
- Colorectal cancer pathogenesis, oncogenic signaling networks and targeted therapeutic advances.Molecular biomedicine · 2026Review
- Article
- From mono- to multi-cellularFrontiers in cell and developmental biology · 2026Review
- Article
- Impact of treatment history on drug resistance of metastatic colorectal cancer organoids.iScience · 2025Article
- Molecular and clinical registry of Chilean patients diagnosed with BRAF-mutated colorectal cancer.Journal of gastrointestinal oncology · 2025Article
- The application of antibody-based agents in cancer therapy based on their mechanisms of action.Fundamental research · 2025Review
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeAcquired resistance to anti-epidermal growth factor receptor (EGFR) inhibitor (EGFRi) therapy in colorectal cancer (CRC) has previously been explained by the model of acquiring new mutations in
methodsWe analyzed paired plasma samples from patients with
resultsPatients whose tumors were treated with and responded to EGFRi alone were more likely to develop acquired mutations (46%) compared with those treated in combination with cytotoxic chemotherapy (9%). Furthermore, contrary to the generally accepted hypothesis of the clonal evolution of acquired resistance, we demonstrate that baseline resistant subclonal mutations rarely expanded to become clonal at progression, and most remained subclonal or disappeared. Consistent with this clinical finding, preclinical models with acquired resistance to either cetuximab or chemotherapy were cross-resistant to the alternate agents, with transcriptomic profiles consistent with epithelial-to-mesenchymal transition. By contrast, commonly acquired resistance alterations in the MAPK pathway do not affect sensitivity to cytotoxic chemotherapy.
conclusionThese findings support a model of resistance whereby transcriptomic mechanisms of resistance predominate in the presence of active cytotoxic chemotherapy combined with EGFRi, with a greater predominance of acquired MAPK mutations after single-agent EGFRi. The proposed model has implications for prospective studies evaluating EGFRi rechallenge strategies guided by acquired MAPK mutations, and highlights the need to address transcriptional mechanisms of resistance.
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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.