title: Of mice and men: opportunities to use genetically engineered mouse models of synovial sarcoma for preclinical cancer therapeutic evaluation.
abstract: BACKGROUND
  Synovial sarcoma is a soft tissue malignancy with a predilection for adolescents and young adults. Despite recent improvements in the understanding of its character and etiology, few therapeutic advances have been made. The mortality rate is high among the young population it affects. The low incidence of most subtypes of sarcoma, such as synovial sarcoma, makes disease-specific trials difficult to organize. The biological differences between sarcoma subtypes make inclusion of multiple types in general trials unsatisfactory as well.
  
  
  METHODS
  A review of the literature regarding targetable pathways in synovial sarcoma was undertaken. A strategy has been devised to utilize available technologies in order to prioritize drug trial planning.
  
  
  RESULTS
  Cell culture and xenograft research with synovial sarcoma cell lines have identified some critical pathways that may be targetable. Promising therapeutic strategies include newer cytotoxic chemotherapies, antiangiogenic agents, anti-IGF1R pathway agents, anti-Bcl-2/proapoptotic agents, and histone deacetylase complex inhibitors.
  
  
  CONCLUSIONS
  We propose to prioritize potential therapeutic strategies via preclinical testing of agents in a genetic mouse model of synovial sarcoma. Preclinical optimization of treatment regimens can guide the development of more focused patient trials.
authors.affiliation: Department of Orthopaedic Surgery, The Center for Children’s Cancer Research, at The University of Utah, Salt Lake City, Utah, USA.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Jones
authors.forename: Malay
authors.initials: M
authors.lastname: Haldar
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Schiffman
authors.forename: Lisa
authors.initials: L
authors.lastname: Cannon-Albright
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Lessnick
authors.forename: Sunil
authors.initials: S
authors.lastname: Sharma
authors.forename: Mario R
authors.initials: MR
authors.lastname: Capecchi
authors.forename: R Lor
authors.initials: RL
authors.lastname: Randall
mesh_terms: D000293:Adolescent; D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D002648:Child; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005818:Genetic Engineering; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy; D013584:Sarcoma, Synovial / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents