HB-EGF orchestrates the complex signals involved in triple-negative and trastuzumab-resistant breast cancer

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Updated: Jun 12, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Fusanori Yotsumoto1, Eiji Oki, Eriko Tokunaga

  • 1Department of Biochemistry, School of Medicine, Fukuoka University, Jonan-ku, Fukuoka, Japan.

International Journal of Cancer
|May 26, 2010
PubMed

Insights

A novel therapeutic strategy targeting heparin-binding epidermal growth factor-like growth factor (HB-EGF) shows promise for treating resistant breast cancers. This approach using crossreacting material 197 (CRM197) inhibits tumor growth and induces apoptosis in triple-negative and trastuzumab-resistant breast cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Current breast cancer therapies targeting the epidermal growth factor receptor (EGFR) have limitations.
  • Trastuzumab-resistant and triple-negative breast cancer (TNBC) remain challenging to treat.
  • Heparin-binding epidermal growth factor-like growth factor (HB-EGF), an EGFR ligand, is highly expressed in breast cancer.

Purpose of the Study:

  • To investigate HB-EGF as a therapeutic target in breast cancer.
  • To evaluate the efficacy of crossreacting material 197 (CRM197), an HB-EGF inhibitor, in preclinical models.
  • To explore the molecular mechanisms underlying CRM197's anti-cancer effects.

Main Methods:

  • Analysis of HB-EGF expression in breast cancer tissues.
  • Treatment of TNBC and trastuzumab-resistant breast cancer models with CRM197.
  • Assessment of signaling pathway activation (ERK, AKT) and cell apoptosis.
  • Evaluation of tumor growth inhibition in vivo.

Main Results:

  • CRM197 treatment effectively blocked ERK and AKT activation in both TNBC and trastuzumab-resistant breast cancer models.
  • CRM197 induced significant apoptosis in cancer cells.
  • CRM197 demonstrated potent inhibition of tumor growth.
  • The drug acted via complexes of EGFR with unknown receptors in TNBC and EGFR/HER2 in resistant cancer.

Conclusions:

  • HB-EGF represents a rational and novel molecular target for breast cancer therapy.
  • CRM197 is a potential anticancer agent for molecularly targeted therapies, particularly for resistant and TNBC.
  • Targeting specific EGFR ligands offers a new avenue for overcoming therapeutic resistance in breast cancer.

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