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Updated: Jun 18, 2026

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer
09:08

Integration of Bioinformatics Approaches and Experimental Validations to Understand the Role of Notch Signaling in Ovarian Cancer

Published on: January 12, 2020

Notch pathway as candidate therapeutic target in Her2/Neu/ErbB2 receptor-negative breast tumors

Hajime Hirose1, Hideshi Ishii, Koshi Mimori

  • 1Department of Gastrointestinal Surgery, Osaka University School of Medicine, Yamadaoka, Osaka, Japan.

Oncology Reports
|December 4, 2009
PubMed

Insights

Targeting the Notch pathway may offer a new therapeutic strategy for Her2-negative breast cancer. Inhibiting Notch signaling sensitizes cancer cells, especially those with genomic damage, to radiation therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Her2/neu/erbB2 receptor (Her2) is a target in receptor-positive breast cancer, but therapeutic targets for Her2-negative breast cancer remain largely undefined.
  • The Notch pathway's role in cancer development and treatment resistance is an area of active investigation.

Purpose of the Study:

  • To investigate potential therapeutic targets in Her2-negative breast cancer.
  • To explore the role of the Notch pathway in Her2-negative breast cancer-initiating cell survival and response to genotoxic stress.

Main Methods:

  • Immunohistochemistry was used to evaluate Her2 expression in 48 primary breast cancer tumors.
  • The Notch pathway was studied in the context of genotoxin-induced suppression of breast cancer-initiating cell growth.
  • Notch pathway knockdown was performed to assess its effect on breast cancer cell sensitivity to deionizing radiation.

Main Results:

  • Her2-negative tumors showed a significant association with overexpression of Notch1 and Notch3.
  • Knockdown of the Notch pathway sensitized breast cancer cells to deionizing radiation, inducing cell death.
  • This sensitization was more pronounced in CD44+ stem cells and in Her2-negative compared to Her2-positive cancer cells.

Conclusions:

  • Inhibition of Notch signaling can counteract survival signals in Her2-negative breast cancer-initiating cells with genomic damage.
  • Targeted suppression of the Notch pathway presents a potential therapeutic strategy for sensitizing Her2-negative breast cancer to existing treatments.

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