Caveolin-1 and Sox-2 are predictive biomarkers of cetuximab response in head and neck cancer
| Autor: | Jennifer Bolen, Neil E. Bhola, Stephen B. Keysar, Umamaheswar Duvvuri, Aaron Hechmer, Danielle L. Swaney, Antonio Jimeno, Mohammad Naser, Daniel Johnson, Kelechi Nwachuku, Tian Ran Zhu, Jennifer R. Grandis, Ritu Roy, Nevan J. Krogan, Rex H. Lee, Scott R. VandenBerg, Rachel A. O'Keefe, Adam B. Olshen, Mehdi Bouhaddou, Hua Li, Gordon B. Mills |
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| Rok vydání: | 2021 |
| Předmět: |
Caveolin 1
Cetuximab Antineoplastic Agents Therapeutics Mice Rare Diseases Antineoplastic Agents Immunological Genetics Biomarkers Tumor Medicine Animals Humans Epidermal growth factor receptor Dental/Oral and Craniofacial Disease neoplasms EGFR inhibitors Cancer screening and diagnosis Tumor biology business.industry SOXB1 Transcription Factors Head and neck cancer Human Genome General Medicine medicine.disease Head and neck squamous-cell carcinoma digestive system diseases Detection Immunological Orphan Drug Good Health and Well Being Head and Neck Neoplasms Cancer research biology.protein Biomarker (medicine) business Biomarkers medicine.drug 4.2 Evaluation of markers and technologies Research Article |
| Zdroj: | JCI Insight JCI insight, vol 6, iss 20 |
| ISSN: | 2379-3708 |
| Popis: | The epidermal growth factor receptor (EGFR) inhibitor cetuximab is the only FDA-approved oncogene-targeting therapy for head and neck squamous cell carcinoma (HNSCC). Despite variable treatment response, no biomarkers exist to stratify patients for cetuximab therapy in HNSCC. Here, we applied unbiased hierarchical clustering to reverse-phase protein array molecular profiles from patient-derived xenograft (PDX) tumors and revealed 2 PDX clusters defined by protein networks associated with EGFR inhibitor resistance. In vivo validation revealed unbiased clustering to classify PDX tumors according to cetuximab response with 88% accuracy. Next, a support vector machine classifier algorithm identified a minimalist biomarker signature consisting of 8 proteins - caveolin-1, Sox-2, AXL, STING, Brd4, claudin-7, connexin-43, and fibronectin - with expression that strongly predicted cetuximab response in PDXs using either protein or mRNA. A combination of caveolin-1 and Sox-2 protein levels was sufficient to maintain high predictive accuracy, which we validated in tumor samples from patients with HNSCC with known clinical response to cetuximab. These results support further investigation into the combined use of caveolin-1 and Sox-2 as predictive biomarkers for cetuximab response in the clinic. |
| Databáze: | OpenAIRE |
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