Targeting HER2: a decade of progress in breast and gastric cancer therapy

Abstract

Background: Human epidermal growth factor receptor 2 (HER2) is a key member of the epidermal growth factor receptor family and a crucial driver of tumorigenesis in breast and gastric cancers. HER2 amplification and overexpression are associated with poor prognosis, making HER2 an essential therapeutic target. Over the last two decades, significant advancements in HER2-targeted therapies have transformed the treatment landscape, with numerous monoclonal antibodies, tyrosine kinase inhibitors, and antibody–drug conjugates providing substantial survival benefits. Aim: This review aims to summarize the progress in HER2-targeted therapies for breast and gastric cancer over the past decade, highlighting their mechanisms of action, clinical applications, patient selection, and associated side effects. Materials and methods: A comprehensive literature review was conducted using PubMed, Scopus, and Web of Science databases. Studies published between 2013 and 2023, written in English, and focused on HER2-positive breast or gastric cancers were included. Eligible articles comprised clinical trials, systematic reviews, meta-analyses, and real-world studies that evaluated the mechanism, efficacy, safety, or resistance patterns of HER2-targeted therapies such as trastuzumab, pertuzumab, ado-trastuzumab emtansine (TDM1), trastuzumab deruxtecan (T-DXd), and lapatinib. Exclusion criteria were studies involving HER2-negative cancers, non-human or preclinical research without clinical correlation, case reports, editorials, conference abstracts, and non-English publications without available translations. Results: HER2-targeted therapies have shown remarkable efficacy in both early and advanced stages of HER2-positive breast and gastric cancers. Trastuzumab remains the cornerstone of treatment, while pertuzumab improves outcomes in combination regimens. Antibody–drug conjugates such as T-DM1 and T-DXd offer novel mechanisms to deliver cytotoxic agents directly to cancer cells, improving therapeutic indices and reducing systemic toxicity. Tyrosine kinase inhibitors like lapatinib provide unique advantages in treating brain metastases and overcoming resistance. Conclusion: The last decade has seen tremendous progress in HER2-targeted therapies, revolutionizing the management of HER2-positive breast and gastric cancers. Continued innovation and clinical trials promise to extend these advancements, improving patients’ survival and quality of life. The integration of novel agents, personalized approaches, and enhanced understanding of tumor biology will be instrumental in overcoming current limitations and shaping the future of HER2-targeted cancer therapy.