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Updated: May 3, 2026

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Resistance to human epidermal growth factor receptor type 2-targeted therapies

Jean-Christophe Thery1, Jean-Philippe Spano1, David Azria2

  • 1Department of Medical Oncology, Pitié-Salpetriere Hospital, Paris, France.

European Journal of Cancer (Oxford, England : 1990)
|January 28, 2014
PubMed

Insights

Resistance to HER-2 targeted therapies like trastuzumab and lapatinib is common in breast cancer. This review explores mechanisms of resistance and strategies to overcome it, including new drug combinations.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • HER-2 overexpression is a poor prognostic factor in breast cancer.
  • Trastuzumab and lapatinib are approved HER-2 targeted therapies, but resistance limits efficacy.
  • Newer agents like pertuzumab and T-DM1 show improved survival, highlighting evolving treatment landscapes.

Purpose of the Study:

  • To review molecular mechanisms of resistance to HER-2 targeted therapies.
  • To discuss strategies for overcoming primary and secondary resistance to trastuzumab and lapatinib.
  • To explore novel approaches for enhancing anti-HER-2 treatment efficacy.

Main Methods:

  • Literature review of molecular mechanisms of HER-2 resistance.
  • Analysis of clinical data on resistance patterns to HER-2 inhibitors.
  • Discussion of emerging therapeutic strategies and predictive markers.

Main Results:

  • Tumor cells develop resistance through various molecular adaptations to evade HER-2 inhibition.
  • Primary and secondary resistance significantly impact patient outcomes.
  • Newer therapies and combination strategies show promise in overcoming resistance.

Conclusions:

  • Understanding resistance mechanisms is crucial for effective HER-2 targeted therapy.
  • Combination therapies, predictive markers, and targeting nodal pathways are key strategies.
  • Further research is needed to optimize treatment and improve survival in HER-2 positive breast cancer.
Keywords:
Breast cancerHER-2Resistance

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