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Abstract
Transcription factor nuclear factor-erythroid 2-related factor 2 (NRF2) controls cellular
adaptation to oxidants and electrophiles by inducing antioxidant and detoxification
genes in response to redox stress. NRF2 is negatively regulated by Kelch-like ECH-associated
protein 1 (KEAP1). Tumours from approximately 15% of patients with lung cancer harbour
somatic mutations in KEAP1 that prevent effective NRF2 repression. Recently, two NRF2
mutation 'hot-spots' were identified in approximately 10% of patients with lung cancer,
enabling the transcription factor to evade KEAP1-mediated repression. Somatic mutations
in KEAP1 and NRF2 provide an insight into the molecular mechanisms by which NRF2 is
regulated. Moreover, constitutive NRF2 activation might cause drug resistance in tumours,
and an understanding of how the transcription factor is regulated indicates ways in
which this could be overcome.