title: Biology and patterns of response to EGFR-inhibition in squamous cell cancers of the lung and head & neck.
abstract: 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.
authors.affiliation: Department of Oncology, McMaster University, Juravinski Cancer Centre, 699 Concession Street, 3rd Floor Medical Oncology, Hamilton, ON L8V 5C2, Canada. Electronic address: juergensr@hhsc.ca.
authors.forename: Rosalyn A
authors.initials: RA
authors.lastname: Juergens
authors.affiliation: Department of Radiation Oncology, University of Toronto, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, ON M5G 2M9, Canada. Electronic address: scott.bratman@rmp.uhn.ca.
authors.forename: Scott V
authors.initials: SV
authors.lastname: Bratman
authors.affiliation: Department of Pathology, University Health Network, Department of Laboratory Medicine and Pathobiology, University of Toronto, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, ON M5G 2M9, Canada. Electronic address: ming.tsao@uhn.ca.
authors.forename: Ming-Sound
authors.initials: MS
authors.lastname: Tsao
authors.affiliation: Division of Medical Oncology, University of Ottawa, The Ottawa Hospital Cancer Centre, 501 Smyth Road, Ottawa, ON K1H 8L6, Canada. Electronic address: slaurie@toh.ca.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Laurie
authors.affiliation: Division of Medical Oncology, Western University, London Regional Cancer Program, 790 Commissioners Road East, London ON, Canada. Electronic address: sara.kuruvilla@lhsc.on.ca.
authors.forename: M
authors.initials: M
authors.lastname: Sara Kuruvilla
authors.affiliation: Division of Medical Oncology and Hematology, University of Toronto, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, ON M5G 2M9, Canada. Electronic address: albiruni.razak@uhn.ca.
authors.forename: Albiruni R A
authors.initials: AR
authors.lastname: Razak
authors.affiliation: Division of Medical Oncology and Hematology, University of Toronto, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, ON M5G 2M9, Canada. Electronic address: aaron.hansen@uhn.ca.
authors.forename: Aaron R
authors.initials: AR
authors.lastname: Hansen
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000453:epidemiology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000453:epidemiology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000453:epidemiology; D058990:Molecular Targeted Therapy / Q000379:methods; D009154:Mutation; D018307:Neoplasms, Squamous Cell / Q000188:drug therapy* / Q000453:epidemiology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D047428:Protein Kinase Inhibitors; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Biomarkers; Disease management; EGFR inhibition; Head and neck cancer; Lung cancer; Squamous histology