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2018 ; 109
(4
): 900-911
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NRF2 addiction in cancer cells
#MMPMID29450944
Kitamura H
; Motohashi H
Cancer Sci
2018[Apr]; 109
(4
): 900-911
PMID29450944
show ga
The Kelch-like ECH-associated protein 1/nuclear factor erythroid-derived 2-like 2
(KEAP1-NRF2) system is a pivotal defense mechanism against oxidative and
electrophilic stress. Although transient NRF2 activation in response to stress is
beneficial for health, persistent NRF2 activation in cancer cells has deleterious
effects on cancer-bearing hosts by conferring therapeutic resistance and
aggressive tumorigenic activity on cancer cells. Because NRF2 increases the
antioxidant and detoxification capability of cancer cells, persistently high
levels of NRF2 activity enhance therapeutic resistance of cancer cells. NRF2 also
drives metabolic reprogramming to establish cellular metabolic processes that are
advantageous for cell proliferation in cooperation with other oncogenic pathways.
As a result of these advantages, cancer cells with persistent activation of NRF2
often develop "NRF2 addiction" and show malignant phenotypes leading to poor
prognoses in cancer patients. Inhibition of NRF2 is a promising therapeutic
approach for NRF2-addicted cancers and NRF2 inhibitors are being actively
developed. However, giving systemic NRF2 inhibitors might have undesirable
effects on cancer-bearing hosts, considering the central roles of NRF2 in
cytoprotection. To avoid these side-effects, new therapeutic targets besides NRF2
for NRF2-addicted cancers have been actively explored. This review introduces
recent studies describing the development and characterization of NRF2-addicted
cancers, as well as their potential therapeutic targets. Expected advances in
diagnostic and therapeutic interventions for NRF2-addicted cancers are also
discussed.
|Animals
[MESH]
|Antineoplastic Agents/*pharmacology/*therapeutic use
[MESH]
free
free
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