ArticleProceedings of the National Academy of Sciences of the United States of America2011
Genomic dissection of the epidermal growth factor receptor (EGFR)/PI3K pathway reveals frequent deletion of the EGFR phosphatase PTPRS in head and neck cancers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 2 of them syntheses that pooled it.
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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
52 citing papers in PubMed, 2 syntheses or guidelines pooled it, 103 citations in OpenAlex.
- Prevalence of EGFR Tyrosine Kinase Domain Mutations in Head and Neck Squamous Cell Carcinoma: Cohort Study and Systematic Review.In vivo (Athens, Greece) · 2017Pooled it
- Epidermal growth factor 61A>G polymorphism is associated with risk of hepatocellular carcinoma: a meta-analysis.Genetic testing and molecular biomarkers · 2012Pooled it
- nab-Paclitaxel, cisplatin, and 5-fluorouracil followed by concurrent cisplatin and radiation for head and neck squamous cell carcinoma.Oral oncology · 2016Trial
- Trial
- Nab-paclitaxel-based compared to docetaxel-based induction chemotherapy regimens for locally advanced squamous cell carcinoma of the head and neck.Cancer medicine · 2015Trial
- A Single-Amino-Acid Ligand for LAT1: A Minimalist and Modular Platform for Lysosome-Targeted Degradation of Membrane Proteins.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Molecularly Built Ligands Degrade Membrane Receptors via Enhancing Their Accumulation in Lysosomes.ACS central science · 2025Article
- [Research progress on the mechanisms of resistance to cetuximab targeted therapy in head and neck squamous cell carcinoma].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2025Review
- Review
- Understanding Glycogen Synthase Kinase-3: A Novel Avenue for Alzheimer's Disease.Molecular neurobiology · 2024Review
- The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance.Nature genetics · 2024Article
- ECT2 promotes the occurrence and is a prognostic biomarker of head and neck squamous cell carcinoma.Journal of Cancer · 2024Article
- Identification of Novel Candidate Genes for Familial Thyroid Cancer by Whole Exome Sequencing.International journal of molecular sciences · 2023Article
- KMT2D deficiency drives lung squamous cell carcinoma and hypersensitivity to RTK-RAS inhibition.Cancer cell · 2023Article
- IQGAP1 and RNA Splicing in the Context of Head and Neck via Phosphoproteomics.Journal of proteome research · 2022Article
- High expression of protein tyrosine phosphatase receptor S (PTPRS) is an independent prognostic marker for cholangiocarcinoma.Frontiers in public health · 2022Article
- Review
- Therapeutic Potential of Antibody-Drug Conjugate-Based Therapy in Head and Neck Cancer: A Systematic Review.Cancers · 2021Review
- Precision Medicine Approaches to Overcome Resistance to Therapy in Head and Neck Cancers.Frontiers in oncology · 2021Review
- A highway to carcinogenesis: the role of IQGAP1, a signaling scaffolding protein, in head and neck cancer development.Oncoscience · 2020Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
Abstract
Activation of the PI3K and epidermal growth factor receptor (EGFR) pathway is able to drive oncogenesis in multiple human cancers, including head and neck squamous cell carcinoma. Targeted agents such as cetuximab and erlotinib are currently used in patients with head and neck squamous cell carcinoma, but, in this disease, the genomic alterations that cause pathway activation and determine response to pharmacologic inhibition remain ill-defined. Here, we present a detailed dissection of the EGFR/PI3K pathway, composed of sequencing of the core pathway components, and high-resolution genomic copy number assessment. Mutations were found in PIK3CA (6%), but no point mutations were observed in other pathway genes such as PTEN and EGFR. In contrast, we observed frequent copy number alterations of genes in the pathway, including PIK3CA, EGFR, protein tyrosine phosphatase receptor S (PTPRS), and RICTOR. In total, activating genetic pathway alterations were identified in 74% of head and neck tumors. Importantly, intragenic microdeletions of the EGFR phosphatase PTPRS were frequent (26%), identifying this gene as a target of 19p13 loss. PTPRS loss promoted EGFR/PI3K pathway activation, modulated resistance to EGFR inhibition, and strongly determined survival in lung cancer patients with activating EGFR mutations. These findings have important implications for our understanding of head and neck cancer tumorigenesis and for the use of targeted agents for this malignancy.
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