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Updated: Dec 29, 2025

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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HER2 heterogeneity and resistance to anti-HER2 antibody-drug conjugates

Alberto Ocaña1,2,3, Eitan Amir4, Atanasio Pandiella5,6

  • 1Experimental Therapeutics Unit, Medical Oncology Department, Hospital Clínico San Carlos and IdISSC, Madrid, Spain. alberto.ocana@salud.madrid.org.

Breast Cancer Research : BCR
|February 2, 2020
PubMed
Abstract

Insights

HER2 intratumoral heterogeneity drives resistance to HER2-targeting therapies like trastuzumab emtansine (T-DM1) in breast cancer. Understanding these resistance mechanisms is key to developing novel antibody-drug conjugates (ADCs) like trastuzumab deruxtecan (DS-8201).

Area of Science:

  • Oncology
  • Pharmacology
  • Genetics

Background:

  • HER2 intratumoral heterogeneity is a significant factor in breast cancer treatment resistance.
  • Resistance to anti-HER2 therapies, especially trastuzumab emtansine (T-DM1), is a growing clinical concern.

Purpose of the Study:

  • To review mechanisms of resistance to HER2-targeting antibody-drug conjugates (ADCs) in breast cancer.
  • To discuss the role of HER2 heterogeneity in treatment failure and the development of new therapies.

Main Methods:

  • Literature-based review of clinical studies and biological findings.
  • Analysis of resistance mechanisms to HER2-targeting antibody-drug conjugates.

Main Results:

  • Clinical studies show varied responses to anti-HER2 strategies, particularly ADCs.
  • HER2 heterogeneity contributes to resistance, impacting the efficacy of current treatments.
  • New ADCs, such as trastuzumab deruxtecan (DS-8201), are in development.

Conclusions:

  • Optimizing ADC efficacy requires understanding and overcoming resistance mechanisms.
  • Future clinical implementation of novel ADCs may be improved by addressing HER2 heterogeneity.
Keywords:
ADCsDS-8201HER2 heterogeneityHER2 resistanceT-DM1

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