Research ArticleCancer

Identification of DHODH as a therapeutic target in small cell lung cancer

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Science Translational Medicine  06 Nov 2019:
Vol. 11, Issue 517, eaaw7852
DOI: 10.1126/scitranslmed.aaw7852

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A big step against small cell cancer

Small cell lung cancer is a particularly aggressive tumor subtype, for which no specific targeted treatments are available. Li et al. used a CRISPR screening approach to identify a metabolic vulnerability and determine that small cell lung cancer cells are particularly reliant on the pyrimidine biosynthesis pathway and therefore sensitive to its disruption. The authors then demonstrated that brequinar, a pharmacological inhibitor of a key step in this pathway, is effective against small cell lung cancer in vitro and in multiple mouse models, including patient-derived xenografts.

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