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Updated: Jan 25, 2026

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Towards precision oncology for HER2 blockade in gastroesophageal adenocarcinoma

V Gambardella1, T Fleitas1, N Tarazona2

  • 1Department of Medical Oncology, Biomedical Research Institute INCLIVA, University of Valencia, Valencia.

Annals of Oncology : Official Journal of the European Society for Medical Oncology
|May 3, 2019
PubMed

Insights

Precision medicine for HER2-amplified gastroesophageal adenocarcinoma (GEA) remains challenging. This review explores resistance mechanisms to anti-HER2 therapies and strategies to overcome them for improved patient outcomes.

Area of Science:

  • Oncology
  • Molecular Biology
  • Gastroenterology

Background:

  • Gastroesophageal adenocarcinoma (GEA) is a heterogeneous disease with poor prognosis in advanced stages.
  • HER2-amplified GEA presents unique challenges for precision medicine.
  • Current anti-HER2 therapies offer limited benefit beyond first-line treatment.

Purpose of the Study:

  • To review current treatments for HER2-amplified GEA.
  • To investigate mechanisms of primary and acquired resistance to anti-HER2 agents.
  • To explore strategies for overcoming resistance and novel therapeutic approaches.

Main Methods:

  • Review of translational studies on anti-HER2 agents in GEA.
  • Analysis of molecular and microenvironmental factors influencing treatment response.
  • Examination of clinical outcomes and resistance patterns.

Main Results:

  • Trastuzumab added to chemotherapy improves outcomes but is insufficient alone.
  • Variable HER2 assessment, tumor heterogeneity, and resistance mechanisms limit anti-HER2 efficacy.
  • No other anti-HER2 agents have shown benefit in first-line or later settings.

Conclusions:

  • Identifying resistance factors is crucial for personalized GEA treatment.
  • Overcoming resistance to anti-HER2 therapy requires a multi-faceted approach.
  • Novel anti-HER2 agents and strategies are under development for GEA.
Keywords:
HER2 amplificationdrug resistancegastroesophageal cancernew anti-HER2 drugstumour heterogeneitytumour microenvironment

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