Ewing/PNET (peripheral neuroepithelioma) tumors are rare aggressive bone 
sarcomas occurring in young people. Rare-disease clinical trials can require 
global collaborations and many years. In vivo models that as accurately as 
possible reflect the clinical disease are helpful in selecting therapeutics with 
the most promise of positive clinical impact. Human Ewing/PNET sarcoma cell 
lines developed over the past 45 years are described. Several of these have 
undergone genetic analysis and have been confirmed to be those of Ewing/PNET 
sarcoma. The A673 Ewing sarcoma line has proven to be particularly useful in 
understanding the biology of this disease in the mouse. The chromosomal 
translocation producing the EWS/FLI1 fusion transcript characterizes clinical 
Ewing sarcoma. Cell lines that express this genetic profile are confirmed to be 
those of Ewing sarcoma. The A673 Ewing sarcoma line grows in culture and as a 
xenograft in immunodeficient mice. The A673 model has been used to study Ewing 
sarcoma angiogenesis and response to antiangiogenic agents. Many Ewing sarcoma 
clinical specimens express the cell surface protein endosialin. Several Ewing 
sarcoma cell lines, including the A673 line, also express cell surface 
endosialin when grown as subcutaneous tumor nodules and as disseminated disease; 
thus the A673 is a useful model for the study of endosialin biology and 
endosialin-directed therapies. With the advent of tools that allow 
characterization of clinical disease to facilitate optimal treatment, it becomes 
imperative, especially for rare tumors, to develop preclinical models reflecting 
disease subsets. Ewing PNET sarcomas are a rare disease where models are 
available.