Abstract：
:CIC-DUX4 sarcoma (CDS) is a group of rare, mesenchymal, small round cell tumours that harbour the unique CIC-DUX4 translocation, which causes aberrant gene expression. CDS exhibits an aggressive course and poor clinical outcome, thus novel therapeutic approaches are needed for CDS treatment. Although patient-derived cancer models are an essential modality to develop novel therapies, none currently exist for CDS. Thus, the present study successfully established CDS patient-derived xenografts and subsequently generated two CDS cell lines from the grafted tumours. Notably, xenografts were histologically similar to the original patient tumour, and the expression of typical biomarkers was confirmed in the xenografts and cell lines. Moreover, the xenograft tumours and cell lines displayed high Src kinase activities, as assessed by peptide-based tyrosine kinase array. Upon screening 119 FDA-approved anti-cancer drugs, we found that only actinomycine D and doxorubicin were effectively suppress the proliferation among the drugs for standard therapy for Ewing sarcoma. However, we identified molecular targeting reagents, such as bortezomib and crizotinib that markedly suppressed the growth of CDS cells. Our models will be useful modalities to develop novel therapeutic strategies against CDS.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Oyama R,Takahashi M,Yoshida A,Sakumoto M,Takai Y,Kito F,Shiozawa K,Qiao Z,Arai Y,Shibata T,Araki Y,Endo M,Kawai A,Kondo Tdoi
10.1038/s41598-017-04967-0subject
Has Abstractpub_date
2017-07-05 00:00:00pages
4712issue
1issn
2045-2322pii
10.1038/s41598-017-04967-0journal_volume
7pub_type
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