Xu, Ke; Ma, Jie; Hall, Sean R R; Peng, Ren-Wang; Yang, Haitang; Yao, Feng (2023). Battles against aberrant KEAP1-NRF2 signaling in lung cancer: intertwined metabolic and immune networks. Theranostics, 13(2), pp. 704-723. Ivyspring International 10.7150/thno.80184
|
Text
v13p0704.pdf - Published Version Available under License Creative Commons: Attribution (CC-BY). Download (7MB) | Preview |
The Kelch-like ECH-associated protein 1/nuclear factor erythroid-derived 2-like 2 (KEAP1/NRF2) pathway is well recognized as a key regulator of redox homeostasis, protecting cells from oxidative stress and xenobiotics under physiological circumstances. Cancer cells often hijack this pathway during initiation and progression, with aberrant KEAP1-NRF2 activity predominantly observed in non-small cell lung cancer (NSCLC), suggesting that cell/tissue-of-origin is likely to influence the genetic selection during malignant transformation. Hyperactivation of NRF2 confers a multi-faceted role, and recently, increasing evidence shows that a close interplay between metabolic reprogramming and tumor immunity remodelling contributes to its aggressiveness, treatment resistance (radio-/chemo-/immune-therapy) and susceptibility to metastases. Here, we discuss in detail the special metabolic and immune fitness enabled by KEAP1-NRF2 aberration in NSCLC. Furthermore, we summarize the similarities and differences in the dysregulated KEAP1-NRF2 pathway between two major histo-subtypes of NSCLC, provide mechanistic insights on the poor response to immunotherapy despite their high immunogenicity, and outline evolving strategies to treat this recalcitrant cancer subset. Finally, we integrate bioinformatic analysis of publicly available datasets to illustrate the new partners/effectors in NRF2-addicted cancer cells, which may provide new insights into context-directed treatment.
Item Type: |
Journal Article (Review Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Thoraxchirurgie 04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Thoracic Surgery 04 Faculty of Medicine > Faculty Institutions > Teaching Staff, Faculty of Medicine |
UniBE Contributor: |
Peng, Ren-Wang, Yang, Haitang |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
1838-7640 |
Publisher: |
Ivyspring International |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
18 Jan 2023 13:21 |
Last Modified: |
22 Apr 2024 08:05 |
Publisher DOI: |
10.7150/thno.80184 |
PubMed ID: |
36632216 |
Uncontrolled Keywords: |
KEAP1-NRF2 signaling bioinformatics metabolic reprogramming non-small cell lung cancer therapeutic vulnerabilities tumor immune microenvironment |
BORIS DOI: |
10.48350/177349 |
URI: |
https://boris.unibe.ch/id/eprint/177349 |
Actions (login required)
 |
Edit item |