Related Experiment Video

Updated: Aug 24, 2025

Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material

Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material

Published on: August 1, 2018

Nrf2 Modulation in Breast Cancer

Somayyeh Ghareghomi¹, Mehran Habibi-Rezaei^2,3, Marzia Arese⁴

¹Institute of Biochemistry and Biophysics, University of Tehran, Tehran 1417466191, Iran.

|October 27, 2022

Abstract:

Reactive oxygen species (ROS) are identified to control the expression and activity of various essential signaling intermediates involved in cellular proliferation, apoptosis, and differentiation. Indeed, ROS represents a double-edged sword in supporting cell survival and death. Many common pathological processes, including various cancer types and neurodegenerative diseases, are inflammation and oxidative stress triggers, or even initiate them. Keap1-Nrf2 is a master antioxidant pathway in cytoprotective mechanisms through Nrf2 target gene expression. Activation of the Nfr2 pathway benefits cells in the early stages and reduces the level of ROS. In contrast, hyperactivation of Keap1-Nrf2 creates a context that supports the survival of both healthy and cancerous cells, defending them against oxidative stress, chemotherapeutic drugs, and radiotherapy. Considering the dual role of Nrf2 in suppressing or expanding cancer cells, determining its inhibitory/stimulatory position and targeting can represent an impressive role in cancer treatment. This review focused on Nrf2 modulators and their roles in sensitizing breast cancer cells to chemo/radiotherapy agents.

Insights

Reactive oxygen species (ROS) impact cell survival and death. This review explores Nrf2 pathway modulators for sensitizing breast cancer cells to therapy.

Area of Science:

Biochemistry and Molecular Biology
Cell Biology
Oncology

Background:

Reactive oxygen species (ROS) are crucial signaling molecules influencing cellular processes like proliferation, apoptosis, and differentiation.
Oxidative stress and inflammation are implicated in various pathologies, including cancer and neurodegenerative diseases.
The Keap1-Nrf2 pathway is a key regulator of antioxidant responses, balancing cell survival and death.

Purpose of the Study:

To review the dual role of the Nrf2 pathway in cancer progression and suppression.
To investigate Nrf2 modulators for their potential in cancer therapy.
To focus on sensitizing breast cancer cells to chemotherapy and radiotherapy agents.

Main Methods:

Literature review of studies on ROS, oxidative stress, and the Keap1-Nrf2 pathway.
Analysis of Nrf2 pathway activation and its impact on cancer cell survival.
Examination of Nrf2 modulators and their effects on chemo/radiotherapy sensitivity.

Main Results:

Nrf2 pathway activation can be protective in early cancer stages by reducing ROS.
Hyperactivation of Keap1-Nrf2 can promote cancer cell survival against oxidative stress and treatments.
Targeting Nrf2 presents a potential strategy for enhancing cancer treatment efficacy.

Conclusions:

The Nrf2 pathway has a complex, context-dependent role in cancer.
Modulating Nrf2 activity offers a promising therapeutic avenue for breast cancer treatment.
Further research into specific Nrf2 modulators is warranted to optimize cancer therapy.

Read full analysis

Keywords:

Keap1-Nrf2 Nrf2 inhibitors antioxidant pathway breast cancer oxidative stress

More Related Videos

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment

Published on: June 9, 2023

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

Published on: March 17, 2016

Related Concept Videos

Transducer Mechanism: Nuclear Receptors

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:

Mitogens and the Cell Cycle

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...

mTOR Signaling and Cancer Progression

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...

NF-κB-dependent Signaling Pathway

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...

Abnormal Proliferation

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...

Adaptive Mechanisms in Cancer Cells

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...

Articles linked to this work by shared authors, journal, and citation graph.

Mechanistic insights into the inhibition of insulin amyloidogenesis and associated toxicity by the p.M14L variant of exenatide.

The FEBS journal·2026

Recent advancements in NRF2-regulated ferroptosis modulation for targeted cancer therapy.

Molecular biology reports·2026

Correction: Tber et al. Pyrido[2',1':2,3]imidazo[4,5-c]isoquinolin-5-amines as Potential Cytotoxic Agents Against Human Neuroblastoma. Pharmaceuticals 2021, 14, 750.

Pharmaceuticals (Basel, Switzerland)·2026

Obesity-associated unfolded protein response, oxidative stress, and NRF2 signaling.

International journal of obesity (2005)·2026

Sialic acid-modified phosphorene for low-necrosis and targeted drug delivery in breast cancer.

RSC advances·2026

Anti-fibrillation and trans-fibrillation activities of L-arginine modified magnetic nanoparticles on lysozyme.

Biochemistry and biophysics reports·2026

See all related articles