title: Integration of molecular targeted therapy with radiation in head and neck cancer.
abstract: Approximately 600,000 new cases of head and neck cancer arise worldwide each year. Of these, a large majority are head and neck squamous cell carcinomas (HNSCC). Conventional treatments, including surgical excision followed by radiation and/or chemoradiotherapy have limited efficacy and are associated with substantial toxicity. To date, key targets for molecular targeted therapy in HNSCC are epidermal growth factor receptors and angiogenesis-related factors. Cetuximab is a monoclonal antibody targeting the epidermal growth factor receptor (EGFR) and it is the only targeted therapy approved by the United States Food and Drug Administration for the treatment of HNSCC. Cetuximab in combination with radiotherapy represents a standard approach for newly diagnosed patients who are unable to tolerate platinum chemotherapy. Despite efficacy in preclinical HNSCC models, cetuximab is only effective in a subset of HNSCC patients, most likely due to the high heterogeneity of this cancer. Additional targets under active investigation include the PI3K/Akt pathway, the Ras-MAPK-ERK pathway and the JAK/STAT pathway, among others. Combining molecular targeted therapies and radiation may allow for deintensification of radiotherapy thereby reducing radiation toxicities and improving treatment outcomes. Here we review the preclinical and clinical data in support of treatment strategies that combined targeted therapy with radiation in HNSCC.
authors.affiliation: Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Du
authors.affiliation: Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
authors.forename: Noah D
authors.initials: ND
authors.lastname: Peyser
authors.affiliation: Department of Otolaryngology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. Electronic address: jgrandis@pitt.edu.
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Grandis
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D066246:ErbB Receptors / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D006801:Humans; D058990:Molecular Targeted Therapy; D000077195:Squamous Cell Carcinoma of Head and Neck; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A; D066246:ErbB Receptors
keywords: Clinical trials; Epidermal growth factor receptor; Head and neck squamous cell carcinoma; Molecular targeted therapy; Preclinical models; Radiotherapy