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

Abstract

Human epidermal growth factor receptor 2 (HER2) is a receptor tyrosine kinase that belongs to the human epidermal growth factor receptor family. It is overexpressed/amplified in approximately 20% of gastric or gastroesophageal junction cancers. HER2 is being developed as a therapeutic target in a variety of cancers, and several agents have been shown to be effective in breast cancer. The development of HER2-targeted therapy for gastric cancer successfully began with trastuzumab. However, while effective in breast cancer, the successive anti-HER2 agents lapatinib, T-DM1, and pertuzumab failed to demonstrate benefits regarding survival in gastric cancer compared with the existing standard therapies. Intrinsic differences lie between gastric and breast cancer in terms of HER2-positive tumor biology, which may make development difficult. Recently, a novel anti-HER2 agent, trastuzumab deruxtecan, was introduced, and the development of HER2-positive gastric cancer agents has been moving to the next stage. This review summarizes the current HER2-targeted therapy for gastric or gastroesophageal cancer in chronological order and describes the promising future of HER2-targeted therapy.