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Targeting HER2 in Gastroesophageal Adenocarcinoma: Molecular Features and Updates in Clinical Practice

Maria Bonomi1, Daniele Spada1, Gian Luca Baiocchi2

  • 1Oncology Unit, ASST Cremona, 26100 Cremona, Italy.

International Journal of Molecular Sciences
|April 13, 2024
PubMed

Insights

Treatment for HER2-positive gastroesophageal adenocarcinoma (GEA) is evolving. Trastuzumab remains a standard, while newer therapies like trastuzumab deruxtecan show promise for improving outcomes in GEA.

Area of Science:

  • Oncology
  • Gastroenterology
  • Molecular Biology

Background:

  • Gastroesophageal adenocarcinoma (GEA) is a leading cause of cancer mortality worldwide.
  • Human epidermal growth factor receptor 2 (HER2) overexpression occurs in about 20% of GEA cases, making it a target for therapy.
  • Accurate HER2-positive status identification is critical for effective targeted treatment in GEA.

Purpose of the Study:

  • To review historical and emerging therapeutic strategies for HER2-positive GEA.
  • To discuss the HER2 molecular pathway and its relevance in GEA treatment.
  • To explore the potential of novel blood biomarkers for guiding GEA therapy.

Main Methods:

  • Literature review of clinical trials and research on HER2-positive GEA treatments.
  • Analysis of the HER2 molecular pathway and its role in GEA pathogenesis.
  • Examination of emerging biomarkers, including circulating tumor DNA and cells.

Main Results:

  • The ToGA trial established trastuzumab plus chemotherapy as a first-line standard for HER2-positive GEA.
  • Many other anti-HER2 drugs have shown limited efficacy in advanced GEA compared to breast cancer.
  • Recent advances include trastuzumab combinations and trastuzumab deruxtecan, showing improved outcomes.

Conclusions:

  • HER2-targeted therapy is crucial for managing HER2-positive GEA.
  • While trastuzumab is established, newer agents and combinations are expanding treatment options.
  • Biomarkers like ctDNA and CTCs may offer future personalized treatment guidance for GEA.
Keywords:
HER2ct-DNAgastroesophageal adenocarcinomaheterogeneityimmunotherapytrastuzumabtrastuzumab deruxtecan

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