title: Targeting DDR2 in head and neck squamous cell carcinoma with dasatinib.
abstract: Squamous cell carcinoma of the head and neck (HNSCC) is the tenth most common tumor entity in men worldwide. Nevertheless therapeutic options are mostly limited to surgery and radio-chemotherapy resulting in 5-year survival rates of around 50%. Therefore new therapeutic options are urgently needed. During the last years, targeting of receptor tyrosine kinases has emerged as a promising strategy that can complement standard therapeutical approaches. Here, we aimed at investigating if the receptor tyrosine kinase DDR2 is a targetable structure in HNSCC. DDR2 expression was assessed on a large HNSCC cohort (554 patients) including primary tumors, lymph node metastases and recurrences and normal mucosa as control. Subsequently, DDR2 was stably overexpressed in two different cell lines (FaDu and HSC-3) using lentiviral technology. Different tumorigenic properties such as proliferation, migration, invasion, adhesion and anchorage independent growth were assessed with and without dasatinib treatment using in-vitro cell models and in-vivo zebrafish xenografts. DDR2 was overexpressed in all tumor tissues when compared to normal mucosa. DDR2 overexpression led to increased migration, invasion, adhesion and anchorage independent growth whereas proliferation remained unaltered. Upon dasatinib treatment migration, invasion and adhesion could be inhibited in-vitro and in-vivo whereas proliferation was unchanged. Our data suggest treatment with dasatinib as a promising new therapeutic option for patients suffering from DDR2 overexpressing HNSCC. Since dasatinib is already FDA-approved we propose to test this drug in clinical trials so that patients could directly benefit from this new treatment option.
authors.affiliation: Section of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany.|Institute of Pathology, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: von Mässenhausen
authors.affiliation: Section of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany.|Institute of Pathology, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Sanders
authors.affiliation: Section of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.|Department of Hematology/Oncology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Brägelmann
authors.affiliation: Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Martina
authors.initials: M
authors.lastname: Konantz
authors.affiliation: Section of Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany.|Institute of Pathology, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Angela
authors.initials: A
authors.lastname: Queisser
authors.affiliation: Pathology of the University Medical Center Schleswig-Holstein, Campus Luebeck and the Research Center Borstel, Leibniz Center for Medicine and Biosciences, Luebeck and Borstel, Germany.
authors.forename: Wenzel
authors.initials: W
authors.lastname: Vogel
authors.affiliation: Institute of Pathology, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Glen
authors.initials: G
authors.lastname: Kristiansen
authors.affiliation: Department of Urology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Duensing
authors.affiliation: Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.|Department of Otorhinolaryngology/Head and Neck Surgery, University Hospital of Bonn, Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schröck
authors.affiliation: Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.|Department of Otorhinolaryngology/Head and Neck Surgery, University Hospital of Bonn, Bonn, Germany.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Bootz
authors.affiliation: Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.|Department of Hematology/Oncology, University Hospital of Bonn, Bonn, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Brossart
authors.affiliation: Institute of Pathology, University Hospital of Bonn, Bonn, Germany.|Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Kirfel
authors.affiliation: Department of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Lengerke
authors.affiliation: Pathology of the University Medical Center Schleswig-Holstein, Campus Luebeck and the Research Center Borstel, Leibniz Center for Medicine and Biosciences, Luebeck and Borstel, Germany. sven.perner@uksh.de.
authors.forename: Sven
authors.initials: S
authors.lastname: Perner
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D000069439:Dasatinib / Q000494:pharmacology*; D000070820:Discoidin Domain Receptor 2 / Q000096:biosynthesis*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D000077195:Squamous Cell Carcinoma of Head and Neck; D046888:Tissue Array Analysis; D023041:Xenograft Model Antitumor Assays; D015027:Zebrafish
chemical_list: D000970:Antineoplastic Agents; C000603239:DDR2 protein, human; D000070820:Discoidin Domain Receptor 2; D000069439:Dasatinib
keywords: DDR2; Dasatinib; head and neck cancer; targeted therapy