Related Experiment Video

Updated: Feb 7, 2026

Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
11:34

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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Different Diseases, Different Escapes: Trastuzumab Deruxtecan Resistance in HER2-Amplified versus HER2-Low Breast

Tess A O'Meara1,2,3, Paolo Tarantino1,2,3

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Cancer Discovery
|February 6, 2026
PubMed

Insights

HER2 expression levels influence how well trastuzumab deruxtecan works. This antibody-drug conjugate

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • HER2 (Human Epidermal growth factor Receptor 2) is a key protein in some cancers.
  • Trastuzumab deruxtecan is an antibody-drug conjugate targeting HER2-expressing tumors.

Purpose of the Study:

  • To investigate the relationship between HER2 expression levels and the efficacy of trastuzumab deruxtecan.
  • To explore the mechanisms of resistance to trastuzumab deruxtecan in different HER2 contexts.

Main Methods:

  • Preclinical models (cell lines and animal models) were used to study HER2 internalization and cytotoxicity.
  • Clinical data analysis was performed to assess target dynamics in patients with varying HER2 expression.

Main Results:

  • HER2 expression level directly correlated with trastuzumab deruxtecan internalization and cancer cell killing in preclinical models.
  • Clinical data showed distinct HER2 target dynamics in HER2-low versus HER2-addicted tumors.
  • Mechanisms of resistance varied, including target downregulation in HER2-low disease and payload resistance or mutations in HER2-addicted tumors.

Conclusions:

  • A context-dependent model for HER2-targeted therapy is proposed.
  • Understanding HER2 dynamics is crucial for optimizing antibody-drug conjugate selection and treatment sequencing.
  • Findings have significant implications for personalized cancer treatment strategies.

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