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Updated: Jan 21, 2026

Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
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Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers

Published on: December 5, 2017

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Kinetic Modeling of DUSP Regulation in Herceptin-Resistant HER2-Positive Breast Cancer

Petronela Buiga1,2, Ari Elson2, Lydia Tabernero1

  • 1School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UK.

Genes
|July 31, 2019
PubMed
Abstract

Insights

Inhibiting DUSP16 can re-sensitize Herceptin-resistant HER2-positive breast cancer cells to trastuzumab (Herceptin). Kinetic modeling predicted this effect, guiding new strategies against aggressive breast cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biophysics

Background:

  • HER2-positive breast cancer is aggressive, driven by HER2 overexpression.
  • Trastuzumab (Herceptin) is a standard treatment, but resistance limits efficacy.
  • Dual-specificity phosphatases (DUSPs) regulate HER2 signaling, offering potential therapeutic targets.

Purpose of the Study:

  • To investigate if inhibiting DUSPs can re-sensitize Herceptin-resistant breast cancer cells.
  • To explore the role of DUSP16 in Herceptin resistance.
  • To validate kinetic modeling for predicting therapeutic targets.

Main Methods:

  • Developed kinetic models of HER2 signaling pathways.
  • Simulated various inhibition intensities for DUSPs.
  • Compared model predictions with experimental results from live breast cancer cells.

Main Results:

  • Kinetic modeling showed good agreement with experimental data.
  • DUSP16-silenced cells demonstrated increased responsiveness to Herceptin.
  • A decrease in Herceptin resistance was observed in DUSP16-silenced cells after 72h treatment.

Conclusions:

  • Kinetic modeling of signaling pathways can predict potential therapeutic targets.
  • Inhibiting DUSP16 is a promising strategy to overcome Herceptin resistance in HER2-positive breast cancer.
  • This approach aids experimental research in identifying novel cancer treatment strategies.
Keywords:
Herceptinbreast cancerdual-specificity phosphataseskinetic model

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