Faculty, Staff and Student Publications

Language

English

Publication Date

1-16-2026

Journal

Clinical Cancer Research

DOI

10.1158/1078-0432.CCR-25-1982

PMID

41283902

PMCID

PMC12828793

PubMedCentral® Posted Date

1-24-2026

PubMedCentral® Full Text Version

Author MSS

Abstract

Human epidermal growth factor receptor 2 (HER2) is an established therapeutic target in multiple solid tumors, particularly breast and gastric cancers. Significant advancements have been made in the development of HER2-targeted therapies, including monoclonal antibodies, tyrosine kinase inhibitors, antibody-drug conjugates (ADC), and novel bispecific antibodies. These agents have revolutionized the treatment landscape for HER2-positive metastatic cancers, resulting in improved progression-free and overall survival, and quality of life for patients. Beyond breast and gastric cancers, HER2 expression/amplification has been observed in other solid tumors, such as colorectal, lung, bladder, ovarian, and biliary tract cancers, offering new opportunities for personalized therapy in a larger patient population. In this review, we highlight the current state of HER2-targeted treatment strategies across HER2-expressing solid tumors, discussing the clinical efficacy, adverse event profiles, and challenges of existing therapies. We explore emerging treatment approaches, including novel agents such as HER2-targeting ADCs, combination therapies, and strategies to overcome resistance mechanisms. Additionally, we examine the role of HER2 expression heterogeneity, biomarker-driven patient selection, and diagnostic tools for patient selection and optimization of treatment outcomes. This review also investigates ongoing challenges in expanding HER2-targeted therapies, including addressing intrinsic and acquired resistance and tailoring strategies to low HER2-expressing or HER2-mutant tumors. Lastly, we provide insights into future directions, emphasizing the importance of precision oncology to broaden the therapeutic opportunities of HER2-targeted therapies across diverse HER2-driven malignancies.

Keywords

Humans, Erb-b2 Receptor Tyrosine Kinases, Neoplasms, Molecular Targeted Therapy, Biomarkers, Tumor, Precision Medicine, Protein Kinase Inhibitors

Published Open-Access

yes

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