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Related Concept Videos

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Ribosome Profiling

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Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
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Related Experiment Video

Updated: Apr 8, 2026

An Allele-specific Gene Expression Assay to Test the Functional Basis of Genetic Associations
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The NRF2 readout beyond genotyping†.

Yukako Suzuki1,2,3, Maolin Ge1

  • 1Krantz Family Center for Cancer Research, Massachusetts General Hospital Cancer Center, Charlestown, MA, USA.

The Journal of Pathology
|April 7, 2026
PubMed
Summary

Non-small cell lung cancer (NSCLC) treatment is improved by understanding the Nuclear factor erythroid 2-related factor 2 (NRF2) activation state. Functional readouts, not just mutations, reveal NRF2 hyperactivity and its link to metabolic vulnerabilities.

Keywords:
KEAP1NRF2 activationNSCLCctDNAimmunotherapyliquid biopsymetabolic vulnerability

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Single Cell Analysis Of Transcriptionally Active Alleles By Single Molecule FISH
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Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Non-small cell lung cancer (NSCLC) poses a significant mortality burden, with limited efficacy of current systemic therapies.
  • Focus on Kelch-like ECH-associated protein 1-nuclear factor erythroid 2-related factor 2 (NRF2) axis mutations has not fully captured pathway dysregulation.
  • NRF2 pathway activation state is emerging as a critical determinant of resistance and therapeutic liabilities in NSCLC.

Purpose of the Study:

  • To emphasize the importance of functional readouts for assessing NRF2 pathway activity in NSCLC.
  • To explore the link between NRF2 hyperactivity and context-dependent metabolic liabilities.
  • To outline future clinical translation strategies for NRF2 activation-state stratification.

Main Methods:

  • Review of recent mechanistic and translational studies on the NRF2 pathway in NSCLC.
  • Analysis of the relationship between NRF2 genotype and phenotype using functional readouts.
  • Investigation of metabolic consequences of NRF2 hyperactivity.

Main Results:

  • NRF2 activation state, assessed functionally, is a more accurate indicator of pathway dysregulation than mutation status alone.
  • NRF2 hyperactivity is associated with context-dependent metabolic liabilities.
  • Genotype-phenotype correlation is crucial for defining NRF2 hyperactivity.

Conclusions:

  • Anchoring genotype to phenotype via functional readouts is essential for understanding NRF2 hyperactivity in NSCLC.
  • NRF2 hyperactivity presents context-specific metabolic vulnerabilities that can be therapeutically exploited.
  • Future clinical strategies should include NRF2 activation-state stratification, immune context integration, and redox/metabolic biomarker evaluation.