title: G-Protein-Coupled Receptors: Next Generation Therapeutic Targets in Head and Neck Cancer?
abstract: Therapeutic outcome in head and neck squamous cell carcinoma (HNSCC) is poor in most advanced cases. To improve therapeutic efficiency, novel therapeutic targets and prognostic factors must be discovered. Our studies have identified several G protein-coupled receptors (GPCRs) as promising candidates. Significant epigenetic silencing of GPCR expression occurs in HNSCC compared with normal tissue, and is significantly correlated with clinical behavior. Together with the finding that GPCR activity can suppress tumor cell growth, this indicates that GPCR expression has potential utility as a prognostic factor. In this review, we discuss the roles that galanin receptor type 1 (GALR1) and type 2 (GALR2), tachykinin receptor type 1 (TACR1), and somatostatin receptor type 1 (SST1) play in HNSCC. GALR1 inhibits proliferation of HNSCC cells though ERK1/2-mediated effects on cell cycle control proteins such as p27, p57, and cyclin D1, whereas GALR2 inhibits cell proliferation and induces apoptosis in HNSCC cells. Hypermethylation of GALR1, GALR2, TACR1, and SST1 is associated with significantly reduced disease-free survival and a higher recurrence rate. Although their overall activities varies, each of these GPCRs has value as both a prognostic factor and a therapeutic target. These data indicate that further study of GPCRs is a promising strategy that will enrich pharmacogenomics and prognostic research in HNSCC.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Jichi Medical University, Shimotsuke 329-0498, Japan. kanatake@omiya.jichi.ac.jp.|Laboratory of Head and Neck Center Biology, Department of Otolaryngology, Head and Neck Surgery, the University of Michigan, Ann Arbor, MI 48109, USA. kanatake@omiya.jichi.ac.jp.
authors.forename: Takeharu
authors.initials: T
authors.lastname: Kanazawa
authors.affiliation: Laboratory of Head and Neck Center Biology, Department of Otolaryngology, Head and Neck Surgery, the University of Michigan, Ann Arbor, MI 48109, USA. kiyoshim@hama-med.ac.jp.|Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu 431-319, Japan. kiyoshim@hama-med.ac.jp.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Misawa
authors.affiliation: Laboratory of Head and Neck Center Biology, Department of Otolaryngology, Head and Neck Surgery, the University of Michigan, Ann Arbor, MI 48109, USA. mswyuki8@hama-med.ac.jp.|Department of Otolaryngology/Head and Neck Surgery, Hamamatsu University School of Medicine, Hamamatsu 431-319, Japan. mswyuki8@hama-med.ac.jp.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Misawa
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Medicine, University of the Ryukyus, Nishihara 903-0215, Japan. yataikyue@hotmail.co.jp.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Uehara
authors.affiliation: Department of Head and Neck, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan. hfukusima@jfcr.or.jp.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Fukushima
authors.affiliation: Department of Neurosurgery, Jichi Medical University Saitama Medical Center, Saitama 330-8503, Japan. gkusaka@omiya.jichi.ac.jp.
authors.forename: Gen
authors.initials: G
authors.lastname: Kusaka
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Jichi Medical University, Shimotsuke 329-0498, Japan. maruta@jichi.ac.jp.
authors.forename: Mikiko
authors.initials: M
authors.lastname: Maruta
authors.affiliation: Laboratory of Head and Neck Center Biology, Department of Otolaryngology, Head and Neck Surgery, the University of Michigan, Ann Arbor, MI 48109, USA. careyte@med.umich.edu.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Carey
mesh_terms: D019004:Galanin / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism; D015320:Tachykinins / Q000378:metabolism
chemical_list: D043562:Receptors, G-Protein-Coupled; D015320:Tachykinins; D013004:Somatostatin; D019004:Galanin
keywords: biomarker; head and neck neoplasm; molecular targeted therapy; treatment