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Updated: Aug 4, 2025

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HER2 Targeting in Esophagogastric Cancer: Redefining the Landscape and Breaking Barriers

Samuel L Cytryn1, Yelena Y Janjigian1

  • 1Memorial Sloan Kettering Cancer Center, New York, New York.

Journal of the National Comprehensive Cancer Network : JNCCN
|April 4, 2023
PubMed

Insights

HER2-positive esophagogastric cancer (EGC) treatment has advanced significantly. New therapies like dual HER2 and PD-1 blockade and trastuzumab deruxtecan offer improved survival and a more optimistic outlook.

Area of Science:

  • Oncology
  • Gastroenterology
  • Immunotherapy

Background:

  • HER2 overexpression occurs in about 20% of esophagogastric cancer (EGC) cases.
  • Trastuzumab, an anti-HER2 antibody, improved survival in EGC patients in 2010, marking the first targeted therapy.
  • EGC's aggressive nature and complex biology have historically hindered treatment advancements.

Purpose of the Study:

  • To review the evolving landscape of HER2-positive EGC treatment.
  • To highlight recent therapeutic breakthroughs and their impact on patient outcomes.

Main Methods:

  • Review of clinical trials and FDA approvals for HER2-positive EGC.
  • Analysis of novel therapeutic strategies including antibody-drug conjugates and immunotherapy.

Main Results:

  • Two new FDA approvals within the past two years for HER2-positive EGC.
  • Successful incorporation of dual HER2 and PD-1 blockade strategies.
  • Emergence of trastuzumab deruxtecan, a potent antibody-drug conjugate, showing significant efficacy.

Conclusions:

  • The management of HER2-positive EGC is undergoing rapid transformation.
  • Recent advancements have led to a more optimistic prognosis for patients with HER2-positive EGC.
  • Dual blockade and novel antibody-drug conjugates represent significant progress in EGC therapy.
Keywords:
Esophageal cancerHER2 therapygastric cancer

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