ArticleOral oncology2019
PTEN loss is associated with resistance to cetuximab in patients with head and neck squamous cell carcinoma.
Article in Oral oncology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 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
- Prognostic and predictive significance of nuclear HIF1α expression in locally advanced HNSCC patients treated with chemoradiation with or without nimotuzumab.British journal of cancer · 2020Trial
- Trial
- Digital Twins for Targeted Therapy in Head and Neck Cancer: From Molecular Stratification to Resistance-Aware Combination Strategies.Current oncology (Toronto, Ont.) · 2026Review
- Combination AURKA and WEE1 Inhibition Exhibits Efficacy in EGFR or Pan-ERBB Inhibitor-Resistant Head and Neck Squamous Cell Carcinoma.Cancer research communications · 2026Article
- Review
- Drug-tolerant persister cells in head and neck squamous cell carcinoma: Molecular mechanisms and therapeutic opportunities.Translational oncology · 2026Article
- Review
- Review
- Blockade of the PGE2 Pathway Inhibits the Growth of PTEN-Deficient HNSCC Tumors.Molecular cancer therapeutics · 2025Article
- CDK4/6 inhibition to resensitize BRAF/EGFR inhibitor in patient-derived BRAF/PTEN-mutant colon cancer cells.Translational cancer research · 2024Article
- Cetuximab chemotherapy resistance: Insight into the homeostatic evolution of head and neck cancer (Review).Oncology reports · 2024Review
- Article
- Establishment of head and neck squamous cell carcinoma mouse models for cetuximab resistance and sensitivity.Cancer drug resistance (Alhambra, Calif.) · 2023Article
- Article
- Epidermal growth factor receptor signaling in precancerous keratinocytes promotes neighboring head and neck cancer squamous cell carcinoma cancer stem cell-like properties and phosphoinositide 3-kinase inhibitor insensitivity.Molecular carcinogenesis · 2022Article
- EGFR R521K Polymorphism Is Not a Major Determinant of Clinical Cetuximab Resistance in Head and Neck Cancer.Cancers · 2022Article
- Article
- The Right Partner in Crime: Unlocking the Potential of the Anti-EGFR Antibody CetuximabFrontiers in immunology · 2021Review
- Head and neck cancer: the role of anti-EGFR agents in the era of immunotherapy.Therapeutic advances in medical oncology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 6 institutions in 1 country.
Funding
Abstract
introductionCetuximab, a monoclonal antibody to the epidermal growth factor receptor (EGFR), extends survival in combination with standard therapy in head and neck squamous cell carcinoma (HNSCC). However, as effects are modest, and patients experience side effects, a biomarker to predict resistance and personalize therapy is needed. Activation of signaling pathways downstream from receptor tyrosine kinases predicts resistance to such therapies in other cancers. The most common abnormalities downstream from EGFR in HNSCC are in the PI3K pathway, activated via loss of expression of the regulator PTEN, or via PI3K mutation. We studied whether PTEN and/or PI3K abnormalities predict resistance to cetuximab.
methodsTumor PTEN and PIK3CA/PI3K p110α were analyzed in samples from subjects treated on two trials of cetuximab-based therapy for patients with metastatic or recurrent HNSCC: E5397, a randomized trial of cisplatin plus placebo versus cisplatin plus cetuximab; and NCI-8070, a randomized trial of cetuximab plus sorafenib versus cetuximab. In situ quantification of PTEN and PI3K p110 α was performed using the AQUA™ method of quantitative immunofluorescence. PI3KCA hot spot mutations were determined with BEAMing.
resultsFor E5397, in multivariable analysis, PTEN expressing/PIK3CA WT patients tended to improve PFS with cetuximab compared to placebo (N = 48; HR = 0.54, Wald p = 0.0502). High PTEN expression was significantly associated with superior PFS among patients treated on NCI-8070 (N = 37; HR = 0.35, p = 0.008).
conclusionLoss of PTEN expression may be associated with lack of benefit from cetuximab. This analysis is limited by small sample size, and PTEN as a potential predictive biomarker merits validation in larger sample sets.
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