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Updated: Jun 13, 2025
Validated Immunochemical Assay for Comprehensive Determination of the Human Epidermal Growth Factor Receptor 2 Released from and Bound to Cells
Published on: May 9, 2025
Targeting HER2 in solid tumors: Unveiling the structure and novel epitopes
Xinlin Liu1, Yunlong Song2, Panpan Cheng2
1The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao 266071, China; Qingdao Cancer Institute, Qingdao 266071, China.
Abstract:
Human epidermal growth factor receptor-2 (HER2) is overexpressed in various solid tumor types, acting as an established therapeutic target. Over the last three decades, the fast-paced development of diverse HER2-targeted agents, notably marked by the introduction of the antibody-drug conjugate (ADC), yielding substantial improvements in survival rates. However, resistance to anti-HER2 treatments continues to pose formidable challenges. The complex structure and dynamic dimerization properties of HER2 create significant hurdles in the development of novel targeted therapeutics. In this review, we synthesize the latest insights into the structural intricacies of HER2 and present an unprecedented overview of the epitope characteristics of HER2-targeted antibodies and their derivatives. Furthermore, we delve into the correlation between anti-HER2 antibody binding epitopes and their respective functions, with a particular focus on their efficacy against resistant tumors. In addition, we highlight the potential of emerging anti-HER2 agents that target specific sites or non-overlapping epitopes, poised to transform the therapeutic landscape for HER2-positive tumors in the foreseeable future.
Insights
This review explores Human Epidermal Growth Factor Receptor-2 (HER2) targeted therapies, focusing on antibody-drug conjugates (ADCs) and strategies to overcome treatment resistance by analyzing HER2 structure and antibody epitopes.
Area of Science:
- Oncology
- Molecular Biology
- Immunology
Background:
- Human Epidermal Growth Factor Receptor-2 (HER2) is a key target in solid tumors, with HER2-targeted therapies significantly improving survival.
- Resistance to current anti-HER2 treatments remains a major clinical challenge.
- The complex structure and dimerization of HER2 present difficulties for developing new targeted drugs.
Purpose of the Study:
- To review the structural intricacies of HER2.
- To provide an overview of epitope characteristics for HER2-targeted antibodies and their derivatives.
- To explore the link between antibody epitopes, function, and efficacy in resistant tumors.
Main Methods:
- Literature review synthesizing current research on HER2 structure and targeted therapies.
- Analysis of epitope characteristics of HER2-targeted antibodies.
- Correlation of epitope binding with therapeutic efficacy, especially in resistant HER2-positive cancers.
Main Results:
- Detailed insights into HER2 structural dynamics and dimerization.
- Comprehensive mapping of HER2 antibody epitopes and their functional implications.
- Evidence linking specific epitopes to improved outcomes in resistant HER2-positive tumors.
Conclusions:
- Understanding HER2 structure and antibody epitopes is crucial for developing effective therapies.
- Targeting specific or non-overlapping epitopes offers potential to overcome resistance.
- Emerging anti-HER2 agents targeting unique sites may revolutionize treatment for HER2-positive cancers.
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