Evidence map›Paper›PMID 34020028›Full record

ReviewSeminars in cancer biology2021

The intricacies of NRF2 regulation in cancer.

Cody J Schmidlin, Aryatara Shakya, Matthew Dodson, Eli Chapman, Donna D Zhang

Open access · greenAbstract readReview
In one paragraph

Review in Seminars in cancer biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed, 2 pooled it
5.8field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

56 citing papers in PubMed, 2 syntheses or guidelines pooled it, 93 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. Nrf2 signaling pathway and its molecular regulatory mechanism.Journal of Zhejiang University. Science. B · 2026
    Review
  6. Article
  7. Article
  8. Selective targeting of NRF2-high pancreatic ductal adenocarcinoma with an NQO1-activatable prodrug.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  9. Article
  10. Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. mtKO: A dedicated guide RNA library for mitochondria research.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  16. Article
  17. Review
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Cody J SchmidlinDeparment of Pharmacology and Toxicology, University of Arizona, Tucson, AZ, USA.
Aryatara ShakyaDeparment of Pharmacology and Toxicology, University of Arizona, Tucson, AZ, USA.
Matthew DodsonDeparment of Pharmacology and Toxicology, University of Arizona, Tucson, AZ, USA.
Eli ChapmanDeparment of Pharmacology and Toxicology, University of Arizona, Tucson, AZ, USA.
Donna D ZhangDeparment of Pharmacology and Toxicology, University of Arizona, Tucson, AZ, USA; University of Arizona Cancer Center, University of Arizona, Tucson, AZ, USA. Electronic address: dzhang@pharmacy.arizona.edu.
University of Arizona · US

Funding

TRANSPORT OF TRACE METALS IN A POLLUTED AQUIFERP42ES004940 · NIEHS · UNIVERSITY OF ARIZONA · PI Xinxin Ding · 1990 to 2026
$68.1M
SOUTHWEST ENVIRONMENTAL HEALTH SCIENCES CENTERP30ES006694 · NIEHS · UNIVERSITY OF ARIZONA · PI DEAN BILLHEIMER · 1994 to 2026
$36.7M
Training in Environmental Toxicology of Human DiseaseT32ES007091 · NIEHS · UNIVERSITY OF ARIZONA · PI Nathan J Cherrington · 1985 to 2026
$10.7M
NRF Transcription Factors in Environmental Stress and Disease InterventionR35ES031575 · NIEHS · UNIVERSITY OF FLORIDA · PI Donna D Zhang · 2020 to 2026
$7.1M
Redox and Protein Homeostasis in Arsenic TumorigenicityR01ES031463 · NIEHS · UNIVERSITY OF FLORIDA · PI CHAPMAN, ELI · 2020 to 2024
$1.6M
NIEHS NIH HHS P30 ES006694NIEHS NIH HHS P42 ES004940NIEHS NIH HHS R01 ES031463NIEHS NIH HHS R35 ES031575NIEHS NIH HHS T32 ES007091
6 · The paper itself

Abstract

The complex role of NRF2 in the context of cancer continues to evolve. As a transcription factor, NRF2 regulates various genes involved in redox homeostasis, protein degradation, DNA repair, and xenobiotic metabolism. As such, NRF2 is critical in preserving cell function and viability, particularly during stress. Importantly, NRF2 itself is regulated via a variety of mechanisms, and the mode of NRF2 activation often dictates the duration of NRF2 signaling and its role in either preventing cancer initiation or promoting cancer progression. Herein, different modes of NRF2 regulation, including oxidative stress, autophagy dysfunction, protein-protein interactions, and epigenetics, as well as pharmacological modulators targeting this cascade in cancer, are explored. Specifically, how the timing and duration of these different mechanisms of NRF2 induction affect tumor initiation, progression, and metastasis are discussed. Additionally, progress in the discovery and development of NRF2 inhibitors for the treatment of NRF2-addicted cancers is highlighted, including modulators that inhibit specific NRF2 downstream targets. Overall, a better understanding of the intricate nature of NRF2 regulation in specific cancer contexts should facilitate the generation of novel therapeutics designed to not only prevent tumor initiation, but also halt progression and ultimately improve patient wellbeing and survival.

Indexed as

AnimalsCell Transformation, NeoplasticGene Expression Regulation, NeoplasticHumansNeoplasmsNF-E2-Related Factor 2NF-E2-Related Factor 2CarcinogenesisChemopreventionChemoresistanceKEAP1NRF2

Identifiers

PMID34020028
PMCPMC8599504
OpenAlexW3161536731

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.