NQO1
Overview
NQO1 (NAD(P)H:quinone oxidoreductase 1) is a cytosolic flavoprotein that catalyzes the two-electron reduction of quinones, protecting cells from oxidative stress. In cancer pharmacogenomics, NQO1 expression is the strongest predictor of sensitivity to Hsp90 inhibitors such as 17-AAG (tanespimycin), because NQO1 activates the drug via bioreductive metabolism.
Alterations observed in the corpus
- NQO1 expression was identified as the top predictive biomarker for sensitivity to 17-AAG (Hsp90 inhibitor) across 947 cancer cell lines in the Cancer Cell Line Encyclopedia (CCLE) pharmacogenomic profiling study PMID:22460905
- In HCC, NQO1 acts as a modifier of HSP90-inhibitor (17-AAG/17-DMAG) sensitivity rather than a driver. GI50 for 17-AAG/17-DMAG inversely correlated with NQO1 expression across 29 liver cancer cell lines (Pearson r=−0.56, P=0.0015). Two of three KEAP1-mutant lines were highly sensitive; resistance in the third (MHCC97H) was due to homozygous NQO1 P187S (NQO1*2, rs1800566) which destabilises NQO1 protein. PMID:25822088
Cancer types (linked)
- Pan-cancer cell line panel (947 lines, multiple lineages): NQO1 expression correlates with 17-AAG sensitivity PMID:22460905
Co-occurrence and mutual exclusivity
- NQO1 expression level was assessed as an independent feature from mutational data in the CCLE pharmacogenomic analysis PMID:22460905
Therapeutic relevance
- High NQO1 expression is the top predictor of response to 17-AAG (tanespimycin, Hsp90 inhibitor) in the CCLE dataset; NQO1 activates the drug via bioreductive metabolism PMID:22460905
Open questions
- Whether NQO1 expression is sufficient as a single biomarker to select patients for 17-AAG treatment in clinical settings requires further validation PMID:22460905
Sources
This page was processed by crosslinker on 2026-05-14. - PMID:25822088
This page was processed by crosslinker on 2026-05-14.