Functional CRISPR and shRNA Screens Identify Involvement of Mitochondrial Electron Transport in the Activation of Evofosfamide

Evofosfamide (TH-302) is a hypoxia-activated DNA-crosslinking prodrug currently in clinical development for cancer therapy. Oxygen-sensitive activation of evofosfamide depends on one-electron reduction, yet the reductases that catalyze this process in tumors are unknown. We used RNA sequencing, whol...

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Veröffentlicht in:	Molecular pharmacology 2019-06, Vol.95 (6), p.638-651
Hauptverfasser:	Hunter, Francis W., Devaux, Jules B.L., Meng, Fanying, Hong, Cho Rong, Khan, Aziza, Tsai, Peter, Ketela, Troy W., Sharma, Indumati, Kakadia, Purvi M., Marastoni, Stefano, Shalev, Zvi, Hickey, Anthony J.R., Print, Cristin G., Bohlander, Stefan K., Hart, Charles P., Wouters, Bradly G., Wilson, William R.
Format:	Artikel
Sprache:	eng
Schlagworte:	Cell Line, Tumor Cell Proliferation - drug effects Cell Survival - drug effects CRISPR-Cas Systems Electron Transport - drug effects Gene Expression Regulation - drug effects Gene Regulatory Networks - drug effects HCT116 Cells Humans Mitochondria - drug effects Mitochondria - genetics Neoplasms - drug therapy Neoplasms - genetics Nitroimidazoles - pharmacology Phosphoramide Mustards - pharmacology Prodrugs RNA, Small Interfering - pharmacology Sequence Analysis, RNA - methods
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