Journal
MOLECULAR CANCER THERAPEUTICS
Volume 19, Issue 1, Pages 221-230Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1535-7163.MCT-19-0103
Keywords
-
Categories
Funding
- Intramural Research Program of the NIH, NCI, CCR
- NATIONAL CANCER INSTITUTE [ZIABC011684, ZIABC011761] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Mutations in genes encoding isocitrate dehydrogenases (IDH) 1 and 2 are common cancer-related genetic abnormalities. Malignancies with mutated IDHs exhibit similar pathogenesis, metabolic pattern, and resistance signature. However, an effective therapy against IDH1-mutated solid tumor remains unavailable. In this study, we showed that acquisition of IDH1 mutation results in the disruption of NADP(+)/NADPH balance and an increased demand for glutathione (GSH) metabolism. Moreover, the nuclear factor erythroid 2-related factor 2 (Nrf2) plays a key protective role in IDH1-mutated cells by prompting GSH synthesis and reactive oxygen species scavenging. Pharmacologic inhibition of the Nrf2/GSH pathway via brusatol administration exhibited a potent tumor suppressive effect on IDH1-mutated cancer in vitro and in vivo. Our findings highlight a possible therapeutic strategy that could be valuable for IDH1-mutated cancer treatment.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available