HER2 in solid tumors: microenvironment features and multifaceted advances from mechanisms to clinical translation.
13 affiliations
- 1Department of Pathology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Xuhui District, Shanghai, 200032, China.
- 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
- 3Institute of Pathology, Fudan University, Shanghai, 200032, China.
- 4Department of Artificial Intelligence Medicine, Graduate School of Medicine, Chiba University, Chiba, Japan.
- 5Department of Diagnostic and Interventional Radiology, University of Tsukuba, Tsukuba, Ibaraki, Japan.
- 6Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. [email protected].
- 7Shanghai Urological Cancer Institute, Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, 270 Dong'an Road, Xuhui District, Shanghai, 200032, China. [email protected].
- 8Department of Pathology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Xuhui District, Shanghai, 200032, China. [email protected].
- 9Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. [email protected].
- 10Institute of Pathology, Fudan University, Shanghai, 200032, China. [email protected].
- 11Department of Pathology, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Xuhui District, Shanghai, 200032, China. [email protected].
- 12Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China. [email protected].
- 13Institute of Pathology, Fudan University, Shanghai, 200032, China. [email protected].
Abstract
Human epidermal growth factor receptor 2 (HER2) is a well-established oncogenic driver in multiple solid tumors, most prominently in breast and gastric cancers. Beyond gene amplification-driven signaling through canonical PI3K/AKT and RAS/MAPK pathways, emerging evidence reveals that HER2 functions within a highly dynamic and context-dependent tumor ecosystem. Interactions between HER2-positive tumor cells and immune and stromal compartments actively shape the tumor microenvironment, contributing to immune evasion, therapeutic resistance and disease progression. A central challenge in the clinical management of HER2-altered cancers is pronounced spatial and temporal heterogeneity, which undermines both diagnostic accuracy and the durability of targeted therapies. In response, advances in multi-omics profiling, liquid biopsy technologies and artificial intelligence-assisted analytics are redefining HER2 assessment, shifting it from static tissue-based classification towards dynamic, minimally invasive monitoring. In parallel, the therapeutic landscape has evolved from single-agent HER2 blockade to rational combination strategies. In particular, antibody-drug conjugates have emerged as a transformative modality, extending the therapeutic reach of HER2 targeting beyond traditional indications and offering new opportunities to overcome heterogeneity and drug resistance. This review synthesizes current insights into the molecular and microenvironmental biology of HER2-altered solid tumors and discusses how these advances are reshaping next-generation precision oncology.
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BibTeX
@article{zhang2026her2,
title = {{HER2 in solid tumors: microenvironment features and multifaceted advances from mechanisms to clinical translation.}},
author = {Tianqi Zhang and Cong Tan and Hui Sun and Wenchao Gu and Wenfeng Wang and Midie Xu and Weiqi Sheng},
journal = {Experimental hematology \& oncology},
year = {2026},
month = oct,
doi = {10.1186/s40164-026-00850-9},
url = {https://europepmc.org/article/MED/42958443},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - HER2 in solid tumors: microenvironment features and multifaceted advances from mechanisms to clinical translation.
AU - Tianqi Zhang
AU - Cong Tan
AU - Hui Sun
AU - Wenchao Gu
AU - Wenfeng Wang
AU - Midie Xu
AU - Weiqi Sheng
PY - 2026
DA - 2026/10/28
JO - Experimental hematology & oncology
DO - 10.1186/s40164-026-00850-9
UR - https://europepmc.org/article/MED/42958443
AB - Human epidermal growth factor receptor 2 (HER2) is a well-established oncogenic driver in multiple solid tumors, most prominently in breast and gastric cancers. Beyond gene amplification-driven signaling through canonical PI3K/AKT and RAS/MAPK pathways, emerging evidence reveals that HER2 functions within a highly dynamic and context-dependent tumor ecosystem. Interactions between HER2-positive tumor cells and immune and stromal compartments actively shape the tumor microenvironment, contributing to immune evasion, therapeutic resistance and disease progression. A central challenge in the clinical management of HER2-altered cancers is pronounced spatial and temporal heterogeneity, which undermines both diagnostic accuracy and the durability of targeted therapies. In response, advances in multi-omics profiling, liquid biopsy technologies and artificial intelligence-assisted analytics are redefining HER2 assessment, shifting it from static tissue-based classification towards dynamic, minimally invasive monitoring. In parallel, the therapeutic landscape has evolved from single-agent HER2 blockade to rational combination strategies. In particular, antibody-drug conjugates have emerged as a transformative modality, extending the therapeutic reach of HER2 targeting beyond traditional indications and offering new opportunities to overcome heterogeneity and drug resistance. This review synthesizes current insights into the molecular and microenvironmental biology of HER2-altered solid tumors and discusses how these advances are reshaping next-generation precision oncology.
SN - 2162-3619
ER -