ArticleMolecular oncology2013
Molecular phenotype predicts sensitivity of squamous cell carcinoma of the head and neck to epidermal growth factor receptor inhibition.
Article in Molecular oncology, 2013. 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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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- Evaluation of co‑inhibition of ErbB family kinases and PI3K for HPV‑negative head and neck squamous cell carcinoma.Oncology reports · 2025Article
- Exploring the Therapeutic Implications of Co-Targeting the EGFR and Spindle Assembly Checkpoint Pathways in Oral Cancer.Pharmaceutics · 2024Review
- Multi-kinase compensation rescues EGFR knockout in a cell line model of head and neck squamous cell carcinoma.Archives of oral biology · 2023Article
- Small molecule profiling to define synergistic EGFR inhibitor combinations in head and neck squamous cell carcinoma.Head & neck · 2022Article
- PIK3CA Gene Mutations in HNSCC: Systematic Review and Correlations with HPV Status and Patient Survival.Cancers · 2022Article
- Dacomitinib and gedatolisib in combination with fractionated radiation in head and neck cancer.Clinical and translational radiation oncology · 2021Article
- Combined EGFR1 and PARP1 Inhibition Enhances the Effect of Radiation in Head and Neck Squamous Cell Carcinoma Models.Radiation research · 2020Article
- PRAS40 Phosphorylation Correlates with Insulin-Like Growth Factor-1 Receptor-Induced Resistance to Epidermal Growth Factor Receptor Inhibition in Head and Neck Cancer Cells.Molecular cancer research : MCR · 2020Article
- A Phase 1b Study of Cetuximab and BYL719 (Alpelisib) Concurrent with Intensity Modulated Radiation Therapy in Stage III-IVB Head and Neck Squamous Cell Carcinoma.International journal of radiation oncology, biology, physics · 2020Article
- Rationale for Using Irreversible Epidermal Growth Factor Receptor Inhibitors in Combination with Phosphatidylinositol 3-Kinase Inhibitors for Advanced Head and Neck Squamous Cell Carcinoma.Molecular pharmacology · 2019Article
- Antitumor Efficacy of SLPI Promoter-Controlled Expression of Artificial microRNA Targeting EGFR in a Squamous Cell Carcinoma Cell Line.Pathology oncology research : POR · 2017Article
- PIK3CA hotspot mutations differentially impact responses to MET targeting in MET-driven and non-driven preclinical cancer models.Molecular cancer · 2017Article
- Exceptional response to cetuximab monotherapy in a patient with metastatic oropharyngeal squamous cell carcinoma: a molecular insight.OncoTargets and therapy · 2016Article
- Afatinib efficacy against squamous cell carcinoma of the head and neck cell lines in vitro and in vivo.Targeted oncology · 2015Article
- Genomic Correlate of Exceptional Erlotinib Response in Head and Neck Squamous Cell Carcinoma.JAMA oncology · 2015Article
- Human papillomavirus-associated oropharynx cancer (HPV-OPC): treatment options.Current treatment options in oncology · 2014Review
- mTOR co-targeting in cetuximab resistance in head and neck cancers harboring PIK3CA and RAS mutations.Journal of the National Cancer Institute · 2014Article
- p70S6 kinase is a critical node that integrates HER-family and PI3 kinase signaling networks.Cellular signalling · 2014Article
- Article
- Overcoming cancer cell resistance to VSV oncolysis with JAK1/2 inhibitors.Cancer gene therapy · 2013Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Despite nearly universal expression of the wild-type epidermal growth factor receptor (EGFR) and reproducible activity of EGFR inhibitors in patients with squamous cell carcinoma of the head and neck (SCCHN), the majority of patients will not have objective responses. The mechanisms of this intrinsic resistance are not well established. We hypothesized that sensitivity to EGFR inhibitors can be predicted based on the inhibitors' effects on downstream signaling. Cell viability assays were used to assess sensitivity to the EGFR inhibitor gefitinib (ZD1839) in 8 SCCHN cell lines. Fluorescence in-situ hybridization showed the two most sensitive lines to be highly gene-amplified for EGFR. Western blotting confirmed that phosphoEGFR was inhibited at low concentrations of gefitinib in all lines tested. Phosphorylation of downstream signaling protein AKT was inhibited in sensitive lines while inhibition of phosphoERK displayed no relationship to gefitinib efficacy. Phosphatase and tensin homolog (PTEN) expression was evident in all cell lines. Activating PIK3CA mutations were found in two resistant cell lines where pAKT was not inhibited by gefitinib. In resistant cell lines harboring PIK3CA mutations, a PI3K inhibitor, LY294002, or AKT siRNA reduced cell viability with an additive effect demonstrated in combination with gefitinib. Additionally, LY294002 alone and in combination with gefitinib, was effective at treating PIK3CA mutated tumors xenografted into nude mice. Taken together this suggests that constitutively active AKT is a mechanism of intrinsic gefitinib resistance in SCCHN. This resistance can be overcome through targeting of the PI3K/AKT pathway in combination with EGFR inhibition.
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