Evidence map›Paper›PMID 36551609›Full record

ArticleCancers2022

A New Nrf2 Inhibitor Enhances Chemotherapeutic Effects in Glioblastoma Cells Carrying p53 Mutations.

Rayhaneh Afjei, Negar Sadeghipour, Sukumar Uday Kumar, Mallesh Pandrala, Vineet Kumar, Sanjay V Malhotra, Tarik F Massoud, Ramasamy Paulmurugan

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.6field-weighted citation impact, top 17% 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

13 citing papers in PubMed, 18 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Rayhaneh AfjeiDepartment of Radiology, Molecular Imaging Program at Stanford (MIPS), Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, 3155 Porter Drive, Palo Alto, CA 94305, USA.
Negar SadeghipourDepartment of Radiology, Molecular Imaging Program at Stanford (MIPS), Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, 3155 Porter Drive, Palo Alto, CA 94305, USA.
Sukumar Uday KumarDepartment of Radiology, Molecular Imaging Program at Stanford (MIPS), Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, 3155 Porter Drive, Palo Alto, CA 94305, USA.
Mallesh PandralaDepartment of Radiation Oncology, Stanford University School of Medicine, 3155 Porter Drive, Palo Alto, CA 94305, USA.ORCID 0000-0001-5685-5516
Vineet KumarDepartment of Radiation Oncology, Stanford University School of Medicine, 3155 Porter Drive, Palo Alto, CA 94305, USA.
Sanjay V MalhotraDepartment of Radiation Oncology, Stanford University School of Medicine, 3155 Porter Drive, Palo Alto, CA 94305, USA.ORCID 0000-0003-4056-5033
Tarik F MassoudDepartment of Radiology, Molecular Imaging Program at Stanford (MIPS), Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, 3155 Porter Drive, Palo Alto, CA 94305, USA.
Ramasamy PaulmuruganDepartment of Radiology, Molecular Imaging Program at Stanford (MIPS), Canary Center at Stanford for Cancer Early Detection, Stanford University School of Medicine, 3155 Porter Drive, Palo Alto, CA 94305, USA.ORCID 0000-0001-7155-4738
Stanford University · USOregon Health & Science University · US

Funding

Gary Glazer-GE Fund (Department of Radiology, Stanford University) None.
6 · The paper itself

Abstract

TP53 tumor suppressor gene is a commonly mutated gene in cancer. p53 mediated senescence is critical in preventing oncogenesis in normal cells. Since p53 is a transcription factor, mutations in its DNA binding domain result in the functional loss of p53-mediated cellular pathways. Similarly, nuclear factor erythroid 2-related factor 2 (Nrf2) is another transcription factor that maintains cellular homeostasis by regulating redox and detoxification mechanisms. In glioblastoma (GBM), Nrf2-mediated antioxidant activity is upregulated while p53-mediated senescence is lost, both rendering GBM cells resistant to treatment. To address this, we identified novel Nrf2 inhibitors from bioactive compounds using a molecular imaging biosensor-based screening approach. We further evaluated the identified compounds for their in vitro and in vivo chemotherapy enhancement capabilities in GBM cells carrying different p53 mutations. We thus identified an Nrf2 inhibitor that is effective in GBM cells carrying the p53 (R175H) mutation, a frequent clinically observed hotspot structural mutation responsible for chemotherapeutic resistance in GBM. Combining this drug with low-dose chemotherapies can potentially reduce their toxicity and increase their efficacy by transiently suppressing Nrf2-mediated detoxification function in GBM cells carrying this important p53 missense mutation.

Indexed as

chemotherapyglioblastomaNrf2p53small molecule compounds

Identifiers

PMID36551609
PMCPMC9775980
OpenAlexW4312141311

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.