New Therapeutic Paradigm for Cancers with Activated NRF2

NRF2/NFE2L2 is a pleiotropic transcription factor that orchestrates gene expression in response to xenobiotic and oxidative stress as well as being a central player in metabolic rewiring, inflammation, autophagy, and other cellular processes. Abnormal NRF2 activation, a feature of various cancers, often stems from mutations in its negative regulator KEAP1 and can result in tumors resistant to conventional therapies. In their recent publication, Ding et al. used CRISPR/Cas9-based genetic screening in conjunction with pharmacologic manipulation in murine lung adenocarcinoma (LUAD) cell lines to identify and characterize glucose-6-phosphate dehydrogenase (G6PD), an enzyme in the oxidative pentose phosphate pathway, as a critical downstream effector sustaining KEAP1 mutant cell growth. The authors report that the growth suppression observed in these cells following G6PD inhibition was enhanced by glutaminase inhibition, which interfered with tricarboxylic acid (TCA) pathway anaplerosis. Thus, this study describes the potential therapeutic value of combined G6PD and glutaminase inhibition in patients with KEAP1 mutant cancers.

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Featured GeneTex Products

NRF2 antibody [HL1021] (GTX635826)

KEAP1 antibody [1F10B6] (GTX60660)

RAS (G12D Mutant) antibody [HL10] (GTX635362)

Citrate synthase antibody [N2C3] (GTX110624)