title: Targeting pathways mediating resistance to anti-EGFR therapy in squamous cell carcinoma of the head and neck.
abstract: BACKGROUND
  As epidermal growth factor receptor (EGFR) is overexpressed in approximately 90% of squamous cell carcinomas of the head and neck (SCCHN), several therapeutic agents that target EGFR have been evaluated for the treatment of SCCHN. Although patients with SCCHN derive clinical benefit from anti-EGFR agents, most notably the EGFR monoclonal antibody cetuximab, these patients eventually become resistant to EGFR-based therapies; preclinical studies have shown activation of secondary signaling pathways that lead to resistance to EGFR inhibition and, as such, serve as potential therapeutic targets to overcome resistance to EGFR inhibitors.
  
  
  METHODS
  This review summarizes the results of recently completed trials of anti-EGFR agents in SCCHN, highlights the various mechanisms that drive resistance to EGFR inhibitors in SCCHN, and focuses on several novel targeted agents that could potentially help overcome resistance to EGFR-based therapies in SCCHN. Expert commentary: Due to the development of resistance to EGFR-targeted therapies, novel treatment approaches to overcome resistance are a key unmet need for SCCHN.
authors.affiliation: a Kellogg Cancer Center , NorthShore University HealthSystem , Evanston , IL , USA.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Campbell
authors.affiliation: a Kellogg Cancer Center , NorthShore University HealthSystem , Evanston , IL , USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Hensing
authors.affiliation: a Kellogg Cancer Center , NorthShore University HealthSystem , Evanston , IL , USA.
authors.forename: Mihir K
authors.initials: MK
authors.lastname: Bhayani
authors.affiliation: a Kellogg Cancer Center , NorthShore University HealthSystem , Evanston , IL , USA.
authors.forename: Arif Y
authors.initials: AY
authors.lastname: Shaikh
authors.affiliation: a Kellogg Cancer Center , NorthShore University HealthSystem , Evanston , IL , USA.
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Brockstein
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D015195:Drug Design; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D058990:Molecular Targeted Therapy; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck
chemical_list: D000970:Antineoplastic Agents; D066246:ErbB Receptors
keywords: EGFR; Squamous cell carcinoma of the head and neck; clinical trials; resistance; targeted therapy