Inhibition of the oncogenic fusion protein EWS-FLI1 causes G₂-M cell cycle arrest and enhanced vincristine sensitivity in Ewing's sarcoma.

ABSTRACT: Ewing's sarcoma (ES) is a rare and highly malignant cancer that grows in the bones or surrounding tissues mostly affecting adolescents and young adults. A chimeric fusion between the RNA binding protein EWS and the ETS family transcription factor FLI1 (EWS-FLI1), which is generated from a chromosomal translocation, is implicated in driving most ES cases by modulation of transcription and alternative splicing. The small-molecule YK-4-279 inhibits EWS-FLI1 function and induces apoptosis in ES cells. We aimed to identify both the underlying mechanism of the drug and potential combination therapies that might enhance its antitumor activity. We tested 69 anticancer drugs in combination with YK-4-279 and found that vinca alkaloids exhibited synergy with YK-4-279 in five ES cell lines. The combin

SUBMITTER: Zollner SK 

PROVIDER: S-EPMC7330879 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature