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Updated: Sep 1, 2025

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HER2 Inhibition in Gastric Cancer-Novel Therapeutic Approaches for an Established Target

Caroline Fong1, Ian Chau1

  • 1Gastrointestinal/Lymphoma Unit, The Royal Marsden NHS Foundation Trust, London SW3 6JJ, UK.

Cancers
|August 12, 2022
PubMed

Insights

Human epidermal growth factor receptor 2 (HER2) positive gastric cancer is a significant global health issue. Trastuzumab is a standard treatment, with new antibody-drug conjugates and immune checkpoint inhibitors showing promise for future therapies.

Area of Science:

  • Oncology
  • Gastroenterology
  • Molecular Biology

Background:

  • Gastric cancer is a major cause of cancer mortality worldwide.
  • Human epidermal growth factor receptor 2 (HER2) amplification occurs in 20% of gastric cancers, identifying a targetable patient subset.
  • The ToGA trial established trastuzumab plus chemotherapy as standard first-line care for HER2-positive gastric cancer.

Purpose of the Study:

  • To review the evidence supporting HER2 targeting in gastric cancer.
  • To discuss mechanisms of response and resistance to HER2-directed therapies.
  • To summarize emerging therapies for HER2-positive gastric cancer.

Main Methods:

  • Review of clinical trial data and scientific literature.
  • Analysis of treatment outcomes for HER2-targeted therapies.
  • Discussion of resistance mechanisms and novel therapeutic strategies.

Main Results:

  • Trastuzumab remains a cornerstone of first-line treatment for HER2-positive gastric cancer.
  • Trastuzumab deruxtecan shows efficacy in refractory settings.
  • Combination of trastuzumab, chemotherapy, and immune checkpoint blockade improves response rates.

Conclusions:

  • HER2 targeting is crucial in managing a significant subset of gastric cancers.
  • Emerging therapies like antibody-drug conjugates and immunotherapy are expanding treatment options.
  • Future management of HER2-positive gastric cancer will likely involve novel combinations and targeted agents.
Keywords:
HER2antibody-drug conjugategastric cancerimmunotherapytrastuzumabtrastuzumab deruxtecan

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