title: Xenograft and genetically engineered mouse model systems of osteosarcoma and Ewing's sarcoma: tumor models for cancer drug discovery.
abstract: BACKGROUND
  There are > 75 histological types of solid tumors that are classified into two major groups: bone and soft-tissue sarcomas. These diseases are more prevalent in children, and pediatric sarcomas tend to be highly aggressive and rapidly progressive. Sarcomas in adults may follow a more indolent course, but aggressive tumors are also common. Sarcomas that are metastatic at diagnosis, or recurrent following therapy, remain refractory to current treatment options with dismal overall survival rates. A major focus of clinical trials, for patients with sarcoma, is to identify novel and more effective therapeutic strategies targeted to genomic or proteomic aberrations specific to the malignant cells. Critical to the understanding of the potential for targeted therapies are models of disease that are representative of clinical disease and predictive of relevant clinical responses.
  
  
  METHODS
  In this article, the authors discuss the use of mouse xenograft models and genetically engineered mice in cancer drug discovery. The authors provide a special focus on models for the two most common bone sarcomas: osteosarcoma (OS) and Ewing's sarcoma (ES).
  
  
  CONCLUSIONS
  Predicting whether a new anticancer agent will have a positive therapeutic index in patients with OS and ES remains a challenge. The use of mouse sarcoma models for understanding the mechanisms involved in the response of tumors to new treatments is an important step in the process of drug discovery and the development of clinically relevant therapeutic strategies for these diseases.
authors.affiliation: A.I. duPont Hospital for Children, Cancer Therapeutics Laboratory , 1701 Rockland Rd, Wilmington DE, 19803 , USA.
authors.forename: Valerie B
authors.initials: VB
authors.lastname: Sampson
authors.forename: Davida F
authors.initials: DF
authors.lastname: Kamara
authors.forename: E Anders
authors.initials: EA
authors.lastname: Kolb
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics; D055808:Drug Discovery / Q000379:methods*; D051379:Mice; D008822:Mice, Transgenic; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics; D012512:Sarcoma, Ewing / Q000188:drug therapy* / Q000235:genetics; D012513:Sarcoma, Experimental / Q000188:drug therapy* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents