Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2014
Prognostic biomarkers in phase II trial of cetuximab-containing induction and chemoradiation in resectable HNSCC: Eastern cooperative oncology group E2303.
Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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The trial behind it
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Who cites it
21 citing papers in PubMed, 34 citations in OpenAlex.
- The Effects of Juglone on Cell Proliferation and Insulin-Like Growth Factor I Receptor/Phosphoinositide 3-Kinase/p85 (IGF-IR/PI3K/p85) Signaling Pathway in Pancreatic Cancer.Journal of clinical practice and research · 2025Article
- The Potential microRNA Prognostic Signature in HNSCCs: A Systematic Review.Non-coding RNA · 2023Review
- p-mTOR, p-ERK and PTEN Expression in Tumor Biopsies and Organoids as Predictive Biomarkers for Patients with HPV Negative Head and Neck Cancer.Head and neck pathology · 2023Article
- 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
- A Means of Assessing Deep Learning-Based Detection of ICOS Protein Expression in Colon Cancer.Cancers · 2021Article
- Proteogenomic insights into the biology and treatment of HPV-negative head and neck squamous cell carcinoma.Cancer cell · 2021Article
- The Role of Akt in Acquired Cetuximab Resistant Head and Neck Squamous Cell Carcinoma: AnFrontiers in oncology · 2021Article
- Adaptive ERK signalling activation in response to therapy and in silico prognostic evaluation of EGFR-MAPK in HNSCC.British journal of cancer · 2020Article
- Computer-assisted image analysis of the tumor microenvironment on an oral tongue squamous cell carcinoma tissue microarray.Clinical and translational radiation oncology · 2019Article
- PTEN loss is associated with resistance to cetuximab in patients with head and neck squamous cell carcinoma.Oral oncology · 2019Article
- Novel genetic alterations and their impact on target therapy response in head and neck squamous cell carcinoma.Cancer management and research · 2019Review
- Leveraging Genomics for Head and Neck Cancer Treatment.Journal of dental research · 2018Review
- Mitogen-activated protein kinase signaling pathway in oral cancer.Oncology letters · 2018Article
- FOXA1 inhibits hepatocellular carcinoma progression by suppressing PIK3R1 expression in male patients.Journal of experimental & clinical cancer research : CR · 2017Article
- Biomarker driven treatment of head and neck squamous cell cancer.Cancers of the head & neck · 2017Review
- Review
- Combination of cetuximab with radio-chemotherapy in patients with esophageal cancer: less is more!Journal of thoracic disease · 2015Article
- Phospho-T356RB1 predicts survival in HPV-negative squamous cell carcinoma of the head and neck.Oncotarget · 2015Article
- Genomic Correlate of Exceptional Erlotinib Response in Head and Neck Squamous Cell Carcinoma.JAMA oncology · 2015Article
- Initiation of esophageal squamous cell carcinoma (ESCC) in a murine 4-nitroquinoline-1-oxide and alcohol carcinogenesis model.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
purposeWe sought to evaluate the correlation between tissue biomarker expression (using standardized, quantitative immunofluorescence) and clinical outcome in the E2303 trial. EXPERIMENTAL
designSixty-three eligible patients with operable stage III/IV head and neck squamous cell cancer (HNSCC) participated in the Eastern Cooperative Oncology Group (ECOG) 2303 phase II trial of induction chemotherapy with weekly cetuximab, paclitaxel, and carboplatin followed by chemoradiation with the same regimen. A tissue microarray (TMA) was constructed and EGF receptor (EGFR), ERK1/2, Met, Akt, STAT3, β-catenin, E-cadherin, EGFR Variant III, insulin-like growth factor-1 receptor, NF-κB, p53, PI3Kp85, PI3Kp110a, PTEN, NRAS, and pRb protein expression levels were assessed using automated quantitative protein analysis (AQUA). For each dichotomized biomarker, overall survival (OS), progression-free survival (PFS), and event-free survival (EFS) were estimated by the Kaplan-Meier method and compared using log-rank tests. Multivariable Cox proportional hazards models were used to estimate HRs and test for significance.
resultsForty-two of 63 patients with TMA data on at least one biomarker were included in the biomarker analysis. Tumor extracellular signal-regulated kinase (ERK)1/2 levels were significantly associated with PFS [HR (low/high), 3.29; P = 0.026] and OS [HR (low/high), 4.34; P = 0.008]. On multivariable Cox regression analysis, ERK1/2 remained significantly associated with OS (P = 0.024) and PFS (P = 0.022) after controlling for primary site (oropharynx vs. non-oropharynx) and disease stage (III vs. IV), respectively. Clustering analysis revealed that clusters indicative of activated RAS/MAPK/ERK and/or PI3K/Akt pathways were associated with inferior OS and/or PFS and maintained significance in multivariable analysis.
conclusionsThese results implicate PI3K/Akt and RAS/MAPK/ERK pathways in resistance to cetuximab-containing chemoradiation in HNSCC. Large prospective studies are required to validate these results.
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