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Updated: Feb 13, 2026

A Model for Perineural Invasion in Head and Neck Squamous Cell Carcinoma
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The NOTCH Pathway in Head and Neck Squamous Cell Carcinoma

T Fukusumi1, J A Califano1

  • 11 Moores Cancer Center, University of California, La Jolla, CA, USA.

Journal of Dental Research
|March 1, 2018
PubMed

Insights

NOTCH1 mutations are common in head and neck squamous cell carcinoma (HNSCC), acting as both a tumor suppressor and oncogene. NOTCH pathway alterations impact HNSCC progression and treatment strategies.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Head and neck squamous cell carcinoma (HNSCC) is frequently associated with NOTCH1 gene mutations.
  • NOTCH1 is the second most mutated gene in HNSCC, after TP53.
  • NOTCH1 mutations can be inactivating, suggesting a tumor suppressor role, but activating mutations are observed in Asian populations.

Purpose of the Study:

  • To review current understanding of NOTCH pathway genes in HNSCC.
  • To explore the bimodal role of NOTCH signaling in HNSCC.
  • To discuss the implications of NOTCH pathway alterations for targeted cancer therapy in HNSCC.

Main Methods:

  • Comprehensive genomic analyses of HNSCC.
  • Review of existing literature on NOTCH family members and HNSCC.
  • Analysis of NOTCH pathway gene expression in HNSCC versus normal tissues.

Main Results:

  • NOTCH1 mutations are prevalent in HNSCC, with a significant impact on patient prognosis.
  • NOTCH pathway genes are upregulated in HNSCC, promoting tumor progression, proliferation, and invasion.
  • NOTCH signaling exhibits a context-dependent, bimodal role in HNSCC (tumor suppressor and oncogene).

Conclusions:

  • NOTCH pathway alterations are critical in HNSCC development and progression.
  • Understanding the dual role of NOTCH is essential for effective HNSCC treatment.
  • Targeted therapies focusing on the NOTCH pathway hold promise for HNSCC patients.
Keywords:
DLLHESHEYJAGTCGAanti-NOTCH therapy

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