Special Issue "The KEAP1-NRF2 Pathway in Cancer"
Deadline for manuscript submissions: closed (20 September 2020).
Interests: Hepatocellular carcinoma; Thyroid hormones; NAFLD/NASH; Metabolic Reprogramming; microRNA; Nrf2-Keap1 pathway; Nuclear receptors
Interests: Gastroesophageal cancer; PDX; targeted therapy; resistance; liver cancer; NRF2
The transcription factor NRF2 is considered as part of the main defense mechanism of the cell against oxidative stress and a major regulator of cell survival. As a result, NRF2 has traditionally been deemed to be a tumor suppressor. However, it is now clear that NRF2 promotes survival not only of normal cells but also of cancer cells, suggesting that activation of NRF2 sustains progression to malignancy. Following the evidence that NRF2 activation is frequent in several human and experimental tumors in multiple tissues, and that genetic ablation of the gene completely prevents cancer development in experimental models, NRF2 has also become a prime candidate for targeted therapy in different tumor types.
While much of the focus has, so far, been on activation of the NRF2–KEAP1 pathway caused by Nrf2 or KEAP1 gene mutations or disruption of NRF2–KEAP1 binding, alternative mechanisms of activation have been proposed which might also play an important role. In HCC, for instance, a recent study shows that NRF2 activity depends on fructosamine-3-kinase (FN3K)—a kinase that triggers protein de-glycation—while another work found that the activity of the KEAP1/NRF2 pathway response is dependent on the histone chaperone facilitates chromatin transcription (FACT) protein. As we develop a better understanding of the molecular complexity underlying the different intracellular responses, we can ultimately hope to devise specific interventions for each of these different signaling mechanisms. This is of great relevance as, unfortunately, specific drugs directly aimed at blocking Nrf2 signaling are not yet available. In terms of therapeutic intervention, it is also of outmost relevance to understand whether distinct mechanisms are involved at different stages of cancer development.
With this Special Issue, we aim to present different contributions that will highlight the role of NRF2 signaling in different types of cancer, covering both basic and more (pre)clinical aspects as well as the current status of NRF2 inhibitors, in the hope of promoting advances in our understanding of targeting this complex pathway in human tumors.
Prof. Dr. Amedeo Columbano
Prof. Dr. Silvia Giordano
Manuscript Submission Information
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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access monthly journal published by MDPI.
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- Nrf2/Keap1 mutation
- NRF2 family
- human cancers
- animal models
- p62 and autophagy
- NRF2-targeted drugs