title: Development of transplantable human chordoma xenograft for preclinical assessment of novel therapeutic strategies.
abstract: BACKGROUND
  Chordomas are rare and indolent bone tumors that arise in the skull base and mobile spine. Distant metastases occur in >20% of cases, but morbidity and mortality are mainly related to local relapses that affect the majority of patients. Standard chemotherapy has modest activity, whereas new targeted therapies (alone or in combination) have some activity in controlling disease progression. However, the scarcity of preclinical models capable of testing in vivo responses to these therapies hampers the development of new medical strategies.
  
  
  METHODS
  In this study, 8 chordoma samples taken from 8 patients were implanted in nude mice. Four engrafted successfully and gave rise to tumor masses that were analyzed histologically, by means of fluorescence in situ hybridization and biochemical techniques. The data relating to each of the mouse tumors were compared with those obtained from the corresponding human tumor.
  
  
  RESULTS
  All 4 engraftments retained the histological, genetic and biochemical features of the human tumors they came from. In one epidermal growth factor receptor(EGFR)-positive xenograft, responsiveness to lapatinib was evaluated by comparing the pre- and post treatment findings. The treatment induced a low-level, heterogeneous switching off of EGFR and its downstream signaling effectors.
  
  
  CONCLUSIONS
  Overall, this model is very close to human chordoma and represents a new means of undertaking preclinical investigations and developing tailored therapies.
authors.forename: Fabio
authors.initials: F
authors.lastname: Bozzi
authors.forename: Giacomo
authors.initials: G
authors.lastname: Manenti
authors.forename: Elena
authors.initials: E
authors.lastname: Conca
authors.forename: Silvia
authors.initials: S
authors.lastname: Stacchiotti
authors.forename: Antonella
authors.initials: A
authors.lastname: Messina
authors.forename: GianPaolo
authors.initials: G
authors.lastname: Dagrada
authors.forename: Alessandro
authors.initials: A
authors.lastname: Gronchi
authors.forename: Pietro
authors.initials: P
authors.lastname: Panizza
authors.forename: Marco A
authors.initials: MA
authors.lastname: Pierotti
authors.forename: Elena
authors.initials: E
authors.lastname: Tamborini
authors.forename: Silvana
authors.initials: S
authors.lastname: Pilotti
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002817:Chordoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D000077341:Lapatinib; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011799:Quinazolines / Q000627:therapeutic use*; D012447:Sacrum / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D011799:Quinazolines; D000077341:Lapatinib; D066246:ErbB Receptors