esearch cer Therapy : Preclinical el Models of Myxoid Liposarcoma Xenografts Mimicking Biological and Pharmacologic Features of R an Tumors

wnloade pose: Myxoid liposarcoma is a common subtype of liposarcoma. It is associated in more than 90% es with the chromosomal translocation t(12;16)(q13;p11) leading to the fusion FUS-CHOP gene responsible for the oncogenic transformation of preadipocytes. Recently the marine natural prodbectedin has shown highly selective activity for myxoid liposarcoma, even in the most aggressive -cell subtype. erimental Design: Fragments of 17 sarcomas were transplanted s.c. in female athymic NCr-nu/nu Xenografts were established and characterized by morphology, fluorescence in situ hybridization is for the translocation and reverse transcriptase-PCR analysis for fusion transcripts. Trabectedin jected i.v. ults: Seven of 17 tumors grew as continuous xenografts, five of them being myxoid liposarcoma of und-cell subtype. The chromosomal rearrangement and fusion transcripts in different passages were me as in the human tumors from which they were derived. The responsiveness to trabectedin in type oid liposarcoma xenografts was as high as in patients. The pathologic response was associated with esence of the FUS-CHOP fusion gene, indicating that the drug does not totally eradicate the disease. II myxoid liposarcoma xenografts seemed much less sensitive to trabectedin, confirming previous l observations. clusions: This study reports for the first time the characterization of human myxoid liposarcoma rafts that adequately mimic the biological and pharmacologic features of the human tumor. These ls offer a useful tool for investigating the mechanism of selectivity of trabectedin, testing new commode binations with this drug and evaluating novel therapies for myxoid liposarcoma. Clin Cancer Res; 16(20); 4958–67. ©2010 AACR.