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EWS/FLI confers tumor cell synthetic lethality to CDK12 inhibition in Ewing sarcoma

ABSTRACT: Many cancer types are driven by oncogenic transcription factors that act by inducing aberrant gene expression programs. Unfortunately, transcription factors have been notoriously difficult to drug. Alternative approaches would be to inhibit the aberrant transcriptional programs indirectly or to identify synthetic lethal dependencies in the context of the transcription factor abnormality. We screened THZ1, a recently reported CDK7/12/13 transcriptional inhibitor, in a cancer cell line collection to identify biomarkers of response. EWS/FLI-driven Ewing sarcoma cells were identified to be markedly sensitive to this compound. We determined that the primary target of THZ1 in Ewing sarcoma is CDK12 using genetic approaches and a new selective CDK12/13 inhibitor, THZ531.

ORGANISM(S): Homo sapiens

PROVIDER: GSE82270 | GEO | 2017/10/18

SECONDARY ACCESSION(S): PRJNA324490

REPOSITORIES: GEO

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