Research ArticlePharmacology

The transcription factor SP3 drives TNF-α expression in response to Smac mimetics

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Science Signaling  29 Jan 2019:
Vol. 12, Issue 566, eaat9563
DOI: 10.1126/scisignal.aat9563

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SP3 is key to Smac mimetic efficacy

Finding drugs that selectively target tumor cells and spare healthy tissue is a challenging goal. Smac mimetic compounds have emerged as promising cancer therapies by blocking anti-apoptotic machinery and inducing the production of the cytokine TNF-α. Beug et al. found not only that the transcription factor SP3 critically mediates the molecular and cellular effects of Smac mimetics but also that it is more abundantly expressed in tumors than in normal tissues from the same patients. These findings suggest that using SP3 as a biomarker may identify patients that will best respond to and tolerate these drugs.