Related Experiment Video

Updated: Jan 29, 2026

Isolating Malignant and Non-Malignant B Cells from lck:eGFP Zebrafish
08:32

Isolating Malignant and Non-Malignant B Cells from lck:eGFP Zebrafish

Published on: February 22, 2019

7.5K

Targeting IDH1-Mutated Malignancies with NRF2 Blockade

Yang Liu, Yanxin Lu, Orieta Celiku

    Journal of the National Cancer Institute
    |February 14, 2019
    PubMed
    Abstract

    Insights

    IDH1 mutations disrupt cell redox balance, creating a dependency on the NRF2 antioxidant pathway. Blocking NRF2 effectively targets IDH1-mutated cancers by disrupting reactive oxygen species (ROS) homeostasis.

    Area of Science:

    • Oncology
    • Cell Biology
    • Biochemistry

    Background:

    • Neomorphic IDH1 mutations disrupt cellular redox balance by increasing reactive oxygen species (ROS) production.
    • The mechanisms by which IDH1-mutant cells maintain ROS homeostasis and potential therapeutic vulnerabilities remain unclear.

    Purpose of the Study:

    • To investigate ROS homeostasis in IDH1-mutated cells.
    • To determine if IDH1-mutant cells exhibit dependency on the NRF2 antioxidant pathway.
    • To evaluate NRF2 inhibition as a therapeutic strategy for IDH1-mutated cancers.

    Main Methods:

    • Investigated ROS homeostasis in wild-type and IDH1-mutated cells.
    • Analyzed NRF2 stability and transcriptional activity.
    • Assessed oxidative DNA damage using NRF2-targeting siRNA.
    • Evaluated the NRF2 inhibitor brusatol in an IDH1-mutated xenograft mouse model.

    Main Results:

    • IDH1-mutated cells demonstrated a dependency on the NRF2 antioxidative pathway.
    • NRF2 blockade disrupted ROS homeostasis, increased oxidative DNA damage, and reduced proliferation in IDH1-mutated cells.
    • Brusatol selectively suppressed tumor progression in vivo in IDH1-mutated xenografts.

    Conclusions:

    • IDH1 mutations reprogram ROS homeostasis, leading to NRF2 pathway dependency for ROS scavenging.
    • NRF2 blockade represents a potential novel therapeutic approach for IDH1-mutated malignancies.

    More Related Videos

    Deep Neuromuscular Blockade Leads to a Larger Intraabdominal Volume During Laparoscopy08:50

    Deep Neuromuscular Blockade Leads to a Larger Intraabdominal Volume During Laparoscopy

    Published on: June 25, 2013

    13.6K
    Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens09:33

    Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens

    Published on: August 25, 2023

    1.6K

    Related Concept Videos

    Mutations01:39

    Mutations

    Overview
    94.5K
    Mutations01:35

    Mutations

    Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
    Chromosomal Alterations Are Large-Scale Mutations
    While point mutations are changes in a single nucleotide in...
    44.5K
    Neuromuscular Junction And Blockade01:29

    Neuromuscular Junction And Blockade

    The site of chemical communication between a motor neuron and a muscle fiber is called the neuromuscular junction (NMJ). The end of the motor neuron at the NMJ divides into a cluster of synaptic end bulbs. The cytoplasm of these bulbs consists of synaptic vesicles enclosing acetylcholine molecules, the principal neurotransmitter released at the NMJ. The region opposite the synaptic bulb that ends in the muscle fiber is called the motor end plate, which has acetylcholine receptors. Within the...
    5.0K
    Viral Mutations00:36

    Viral Mutations

    A mutation is a change in the sequence of bases of DNA or RNA in a genome. Some mutations occur during replication of the genome due to errors made by the polymerase enzymes that replicate DNA or RNA. Unlike DNA polymerase, RNA polymerase is prone to errors because it is not capable of “proofreading” its work. Viruses with RNA-based genomes, like HIV, therefore accrue mutations faster than viruses with DNA-based genomes. Because mutation and recombination provide the raw material...
    39.9K
    Mutation, Gene Flow, and Genetic Drift01:09

    Mutation, Gene Flow, and Genetic Drift

    In a population that is not at Hardy-Weinberg equilibrium, the frequency of alleles changes over time. Therefore, any deviations from the five conditions of Hardy-Weinberg equilibrium can alter the genetic variation of a given population. Conditions that change the genetic variability of a population include mutations, natural selection, non-random mating, gene flow, and genetic drift (small population size).
    64.1K
    Mutations in Microorganisms01:18

    Mutations in Microorganisms

    Mutations are heritable changes in an organism’s genome involving alterations in the base sequence of DNA or RNA. These changes can influence cellular processes and phenotypic traits, potentially transforming the unaltered wild type into a mutant form. Such changes, termed forward mutations, are pivotal in shaping the genetic diversity of organisms.RNA viruses exhibit the highest mutation rates due to the absence of robust proofreading mechanisms during genome replication. In contrast,...
    717