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History and Future of HER2-Targeted Therapy for Advanced Gastric Cancer

Shin Ariga1

  • 1Department of Medical Oncology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo 060-8638, Japan.

Journal of Clinical Medicine
|May 27, 2023
PubMed

Insights

Human epidermal growth factor receptor 2 (HER2) is a target in gastric cancer. While early therapies showed promise, newer agents have struggled, but novel treatments like trastuzumab deruxtecan offer new hope.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Human epidermal growth factor receptor 2 (HER2) is a receptor tyrosine kinase overexpressed in 20% of gastric and gastroesophageal junction cancers.
  • HER2-targeted therapies have shown success in breast cancer, initiating similar efforts in gastric cancer.

Purpose of the Study:

  • To review the chronological development of HER2-targeted therapies for gastric and gastroesophageal junction cancers.
  • To discuss the challenges and future directions in HER2-targeted treatment for these cancers.

Main Methods:

  • Review of existing literature on HER2-targeted agents in gastric and gastroesophageal junction cancer.
  • Chronological analysis of therapeutic development and clinical trial outcomes.
  • Comparison of HER2-positive tumor biology between gastric and breast cancer.

Main Results:

  • Trastuzumab was the first successful HER2-targeted agent for gastric cancer.
  • Subsequent agents (lapatinib, T-DM1, pertuzumab) did not improve survival compared to standard therapies.
  • Trastuzumab deruxtecan represents a recent advancement, indicating progress in the field.

Conclusions:

  • Intrinsic biological differences between gastric and breast cancer pose challenges for HER2-targeted therapy development.
  • Despite setbacks, novel agents like trastuzumab deruxtecan are advancing HER2-targeted treatment for gastric cancer.
  • The future of HER2-targeted therapy for gastric cancer is promising with ongoing research and development.
Keywords:
HER2gastric cancerheterogeneitytargeted therapy

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