Biology and patterns of response to EGFR-inhibition in squamous cell cancers of the lung and head & neck

Cancer Treat Rev. 2017 Mar;54:43-57. doi: 10.1016/j.ctrv.2017.01.003. Epub 2017 Jan 17.


The identification of common molecular aberrations that drive cancer progression has led to targeted therapies that improve treatment efficacy in many tumor types. Epidermal growth factor receptor (EGFR) inhibitors have been used to treat both lung and head and neck cancers with squamous cell histology. These tumors often show high EGFR expression and/or increased gene copy number, but low incidence of the activating kinase domain mutations common to adenocarcinomas of the lung. In this manuscript, we review clinical trial data on EGFR-inhibitors in the treatment of squamous cell carcinoma (SqCC) of the lung and head and neck (SCCHN), including both efficacy and biomarker analyses. Although some efficacy with use of EGFR inhibitors is observed, the level of benefit varies within and across tumor types, and the predictive capacity of high EGFR protein expression and/or gene amplification, if any, is limited. Due to the lack of candidate biomarkers that consistently predict response to EGFR-inhibitor therapy across treatment setting and class of agent in SqCC of the lung and SCCHN, we explore the biology, genomics and patterns of response to EGFR-inhibitors to inform identification of potential biomarkers, highlighting several key molecules that have shown promise in preclinical studies and clinical trials across multiple cancer sites.

Keywords: Biomarkers; Disease management; EGFR inhibition; Head and neck cancer; Lung cancer; Squamous histology.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / epidemiology
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / epidemiology
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / epidemiology
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / epidemiology
  • Molecular Targeted Therapy / methods
  • Mutation
  • Neoplasms, Squamous Cell / drug therapy*
  • Neoplasms, Squamous Cell / epidemiology
  • Protein Kinase Inhibitors / pharmacology
  • Squamous Cell Carcinoma of Head and Neck
  • Treatment Outcome


  • Antibodies, Monoclonal
  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • EGFR protein, human
  • ErbB Receptors