Basal subtype is predictive for response to cetuximab treatment in patient-derived xenografts of squamous cell head and neck cancer

Int J Cancer. 2017 Sep 15;141(6):1215-1221. doi: 10.1002/ijc.30808. Epub 2017 Jun 21.


Cetuximab is the single targeted therapy approved for the treatment of head and neck cancer (HNSCC). Predictive biomarkers have not been established and patient stratification based on molecular tumor profiles has not been possible. Since EGFR pathway activation is pronounced in basal subtype, we hypothesized this activation could be a predictive signature for an EGFR directed treatment. From our patient-derived xenograft platform of HNSCC, 28 models were subjected to Affymetrix gene expression studies on HG U133+ 2.0. Based on the expression of 821 genes, the subtype of each of the 28 models was determined by integrating gene expression profiles through centroid-clustering with previously published gene expression data by Keck et al. The models were treated in groups of 5-6 animals with docetaxel, cetuximab, everolimus, cis- or carboplatin and 5-fluorouracil. Response was evaluated by comparing tumor volume at treatment initiation and after 3 weeks of treatment (RTV). Tumors distributed over the 3 signature-defined subtypes: 5 mesenchymal/inflamed phenotype (MS), 15 basal type (BA), 8 classical type (CL). Cluster analysis revealed a strong correlation between response to cetuximab and the basal subtype. RTV MS 3.32 vs. BA 0.78 (MS vs. BA, unpaired t-test, p 0.0002). Cetuximab responders were distributed as following: 1/5 in MS, 5/8 in CL and 13/15 in the BA group. Activity of classical chemotherapies did not differ between the subtypes. In conclusion basal subtype was associated with response to EGFR directed therapy in head and neck squamous cell cancer patient-derived xenografts.

Keywords: EGFR; cetuximab; head and neck cancer; molecular subtype; patient-derived xenograft.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Carboplatin / pharmacology
  • Carcinoma, Basal Cell / drug therapy*
  • Carcinoma, Basal Cell / enzymology
  • Carcinoma, Basal Cell / genetics
  • Carcinoma, Basal Cell / pathology
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / enzymology
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Cetuximab / pharmacology*
  • DNA Mutational Analysis
  • Docetaxel
  • ErbB Receptors / genetics
  • Everolimus / pharmacology
  • Fluorouracil / pharmacology
  • Gene Expression
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / enzymology
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / pathology
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mice
  • Mice, Inbred NOD
  • Retrospective Studies
  • Squamous Cell Carcinoma of Head and Neck
  • Taxoids / pharmacology
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • Taxoids
  • Docetaxel
  • Everolimus
  • Carboplatin
  • EGFR protein, human
  • ErbB Receptors
  • Cetuximab
  • Fluorouracil