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Updated: Mar 12, 2026

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
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Nrf2 and Notch Signaling in Lung Cancer: Near the Crossroad

Angelo Sparaneo1, Federico Pio Fabrizio1, Lucia Anna Muscarella1

  • 1Laboratory of Oncology, IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy.

Oxidative Medicine and Cellular Longevity
|November 17, 2016
PubMed

Insights

The transcription factor Nrf2 and Notch pathway crosstalk promotes cancer growth and treatment resistance. Aberrant activation of these pathways, particularly in lung tumors, highlights their role in cancer development and suggests potential therapeutic targets.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Signaling

Background:

  • Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates cellular antioxidant responses and is implicated in tumor progression and treatment resistance.
  • Nrf2 interacts with Antioxidant Response Elements (AREs) to upregulate cytoprotective genes under stress.
  • The Notch pathway influences cell proliferation, homeostasis, and stem cell self-renewal, and its crosstalk with Nrf2 is significant in tumorigenesis.

Purpose of the Study:

  • To review the current understanding of Nrf2 and Notch pathway alterations in lung tumorigenesis.
  • To explore the reciprocal transcriptional regulation between Nrf2 and Notch during cancer development.
  • To identify potential biomarkers and therapeutic targets based on Nrf2-Notch pathway dysregulation.

Main Methods:

  • Literature review of scientific articles focusing on Nrf2, Notch pathways, and lung cancer.
  • Analysis of gene mutation data for NFE2L2, KEAP1, and NOTCH families in tumor datasets.
  • Synthesis of information on the functional interplay between Nrf2 and Notch signaling in cancer.

Main Results:

  • Both Nrf2 and Notch pathways are frequently altered in various cancers, including lung tumors.
  • Aberrant activation of Nrf2 and Notch signaling can synergistically promote neoplastic proliferation, invasion, and metastasis.
  • Mutations in NFE2L2, KEAP1, and NOTCH genes support the critical role of their crosstalk in cancerogenesis.

Conclusions:

  • The aberrant crosstalk between Nrf2 and Notch pathways plays a significant role in lung tumorigenesis and progression.
  • Understanding these pathway interactions is crucial for developing novel therapeutic strategies.
  • Nrf2 and Notch pathway components represent promising targets for cancer biomarkers and treatments.

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