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Review
. 2023 Jan 30:13:1080990.
doi: 10.3389/fonc.2023.1080990. eCollection 2023.

Challenges and future of HER2-positive gastric cancer therapy

Chenzhe Ma  1   2 , Xiao Wang  1   2 , Jiwu Guo  1   2 , Bo Yang  1   2 , Yumin Li  1   2
Affiliations
Review

Challenges and future of HER2-positive gastric cancer therapy

Chenzhe Ma et al. Front Oncol. .

Abstract

Gastric cancer is the fifth most common cancer worldwide, and the treatment of advanced gastric cancer has relatively little progress. With the continuous development of molecularly targeted therapy for tumors, it has been discovered that human epidermal growth factor receptor 2 (HER2) contributes to the poor prognosis and pathogenesis of various cancers. In order to treat HER2-positive advanced gastric cancer, Trastuzumab has emerged as the first first-line targeted medication used in conjunction with chemotherapy. The consequent trastuzumab resistance has become an important issue, and various new HER2-targeted gastric cancer drugs are emerging to address this challenge. This review's primary concern is the drug mechanism of various HER2-positive gastric cancer targeted therapy and fresh techniques of detection.

Keywords: HER2; Her2 resistance; gastric cancer; receptor ErbB-2; trastuzumab.

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Conflict of interest statement

The authors declare that the research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Mechanism of action of agents targeting HER2. Trastuzumab (green) binds to the ECD IV of HER2, thereby inhibiting the HER2 signaling pathway leading to cell cycle arrest; Pertuzumab (orange), which binds to the ECD II and Inhibits dimer formation; Margetuximab, which binds trastuzumab to an altered Fc-γ domain that involved in ADCC; Lapatinib (yellow) directly prevents the PI3K pathway from being activated by binding to the intracellular tyrosine kinase domain of HER2; T-DM1 (red circle)releases the emtansine moiety after the ADC is phagocytosed by lysosomes; T-Dxd (orange triangle), another ADC combining trastuzumab and deruxtecan, a potent topoisomerase I inhibitor; Bispecific antibody ZW25 (purple) binds to both extracellular domains II and IV of HER-2.
Figure 2
Figure 2
HER2/neu testing algorithm.
See this image and copyright information in PMC

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