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Current Treatment Options in Oncology
Published in:

08-03-2025 | Gastric Cancer | REVIEW

Evolving Landscape of HER2-Targeted Therapies for Gastric Cancer Patients

Authors: Lijuan He, Ben Liu, Zhuanfang Wang, Qinying Han, Hao Chen

Published in: Current Treatment Options in Oncology | Issue 4/2025

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Opinion Statement

Gastric cancer (GC) is a deadly disease worldwide, and trastuzumab in combination with chemotherapy has been the standard first-line treatment for HER2-positive GC following the TOGA trial. Besides adjuvant therapy, HER2-directed therapy is widely used as neoadjuvant or translational therapy, and survival benefit even surgical opportunities is seen in these patients. However, resistance is not rare in recent years, and the second-line treatment for trastuzumab beyond progression has received widespread attention in GC. Moreover, current evidence cannot recommend trastuzumab for patients with IHC1+ HER2 low expression GC yet. Researchers are currently investigating whether GC patients with low HER2 expression could also benefit from HER2-directed therapies. In addition to using HER2 as a target for targeted therapy, HER2-mediated targeted delivery of cytotoxic drugs and targeted immunity have made important contributions to overcoming trastuzumab resistance in recent trials. HER2/neu-derived peptide epitopes vaccination and HER2-specific chimeric antigen receptor (CAR) therapy focus on reestablishing anti-tumor immunity in different ways and show significant anti-tumor activity. Other antibodies that target different regions of the HER2 receptor or block key downstream pathways such as AKT or PI3K also offer potential anti-tumor activity against HER2. HER2 use in GC will not be hampered by resistance or low expression and will play a bigger role. We review the current efforts to enable GC patients with trastuzumab-resistant and HER2 low-expressing accessible to HER2 targeted therapy and present our consideration for future HER2 in GC.
Literature
1.
2.
3.
4.
5.
6.
Shitara K, et al. Efficacy of trastuzumab emtansine in Japanese patients with previously treated HER2-positive locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma: A subgroup analysis of the GATSBY study. Asia Pac J Clin Oncol. 2019;16(1):5–13. https://​doi.​org/​10.​1111/​ajco.​13243.CrossRefPubMed
7.
8.
Tokunaga M, et al. Early endpoints of a randomized phase II trial of preoperative chemotherapy with S-1/CDDP with or without trastuzumab followed by surgery for HER2-positive resectable gastric or esophagogastric junction adenocarcinoma with extensive lymph node metastasis: Japan Clinical Oncology Group study JCOG1301C (Trigger Study). Gastric Cancer. 2024;27(3):580–9. https://​doi.​org/​10.​1007/​s10120-024-01467-9.CrossRefPubMed
9.
Hofheinz RD, et al. Trastuzumab in combination with 5-fluorouracil, leucovorin, oxaliplatin and docetaxel as perioperative treatment for patients with human epidermal growth factor receptor 2-positive locally advanced esophagogastric adenocarcinoma: A phase II trial of the Arbeitsgemeinschaft Internistische Onkologie Gastric Cancer Study Group. Int J Cancer. 2021;149(6):1322–31. https://​doi.​org/​10.​1002/​ijc.​33696.CrossRefPubMed
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
Wiedermann U, et al. A phase Ib/II open label study of IMU-131 HER2/Neu peptide vaccine plus cisplatin and either 5-fluorouracil or capecitabine chemotherapy in patients with HER2/Neu overexpressing metastatic or advanced adenocarcinoma of the stomach or gastroesophageal junction. 2019;37(4_suppl):p. TPS176-TPS176. https://​doi.​org/​10.​1200/​JCO.​2019.​37.​4_​suppl.​TPS176.
35.
36.
37.
Shen A, et al. A novel 4–1BB/HER2 bispecific antibody shows potent antitumor activities by increasing and activating tumor-infiltrating T cells. Am J Cancer Res. 2023;13(7):3246–56.PubMedPubMedCentral
38.
39.
40.
41.
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
Peng Z, et al. Efficacy and safety of a novel anti-HER2 therapeutic antibody RC48 in patients with HER2-overexpressing, locally advanced or metastatic gastric or gastroesophageal junction cancer: a single-arm phase II study. Cancer Commun (Lond). 2021;41(11):1173–82. https://​doi.​org/​10.​1002/​cac2.​12214.CrossRefPubMed
54.
55.
56.
57.
58.
59.
60.
61.
62.
63.
64.
65.
66.
67.
68.
69.
70.
71.
72.
73.
74.
75.
76.
77.
78.
79.
80.
81.
82.
83.
84.
85.
86.
87.
88.
89.
90.
91.
92.
93.
94.
95.
96.
97.
98.
99.
100.
101.
102.
103.
104.
105.
106.
107.
108.
Tobias J, et al. Preclinical and Clinical Observations Implying Combination Therapy to Enhance the Efficacy of the Her-2/neu B-Cell Peptide-Based Vaccine HER-Vaxx and to Prevent Immune Evasion. Int J Mol Sci. 2023;25(1). https://​doi.​org/​10.​3390/​ijms25010287.
109.
110.
111.
112.
113.
114.
115.
116.
117.
118.
119.
120.
121.
122.
Metadata
Title
Evolving Landscape of HER2-Targeted Therapies for Gastric Cancer Patients
Authors
Lijuan He
Ben Liu
Zhuanfang Wang
Qinying Han
Hao Chen
Publication date
08-03-2025
Publisher
Springer US
Published in
Current Treatment Options in Oncology / Issue 4/2025
Print ISSN: 1527-2729
Electronic ISSN: 1534-6277
DOI
https://doi.org/10.1007/s11864-025-01300-0

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