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Peer-reviewedCC BY 4.0Oncology Research

Tumor Microenvironment-Mediated Resistance in HER2-Positive Breast Cancer: Recent Advances and Therapeutic Challenges

  • Yutong Zhang1,2
  • Xuanyi Lv1,2
  • Zhihong Deng1,2
  • Rui Zhuo1,2
  • Jie Dong1
  • Qiang Wang1
  • Xuefeng Shi1
  • Sijie Wu1
  • Ulf D. Kahlert3
  • Wenjie Shi2,3
  • Yefang Hu1,2
  • Li Xia4,5
5 affiliations
  1. 1Graduate School, Guangxi University of Chinese Medicine, Nanning, China
  2. 2Department of Breast Surgery, Guilin Municipal Hospital of Traditional Chinese Medicine, Guilin, China
  3. 3Molecular and Experimental Surgery, Clinic for General-, Visceral-, Vascular- and Transplantation Surgery, Medical Faculty and University Hospital Magdeburg, Otto-von-Guericke University, Magdeburg, Germany
  4. 4University Hospital for Gynecology, Pius Hospital, University Medicine Oldenburg, Oldenburg, Germany
  5. 5Department of Dermatology, Guilin People’s Hospital, Guilin, China
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Abstract

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is associated with aggressive disease and poor prognosis. Despite advances in HER2-targeted therapies, resistance remains a major clinical challenge. This review focuses on the mechanisms of resistance to HER2-targeted therapies, with particular emphasis on the tumor microenvironment (TME). The TME, composed of immune cells, cancer-associated fibroblasts (CAFs), and extracellular matrix components, significantly influences therapeutic responses. Immunosuppressive cells such as tumor-associated macrophages (TAMs), regulatory T cells (Tregs), and myeloid-derived suppressor cells (MDSCs) contribute to immune evasion and therapeutic resistance. Additionally, CAFs contribute to resistance by remodeling the extracellular matrix and creating physical barriers that restrict drug delivery and immune cell infiltration. Emerging therapeutic strategies targeting the TME components show promise in overcoming resistance and improving treatment outcomes. The development of predictive biomarkers, particularly those reflecting TME components, and the integration of spatial profiling technologies will be critical in optimizing personalized treatment strategies for HER2-positive breast cancer.

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Cite

BibTeXRIS
BibTeX
@article{zhang2026tumor,
  title = {{Tumor Microenvironment-Mediated Resistance in HER2-Positive Breast Cancer: Recent Advances and Therapeutic Challenges}},
  author = {Yutong Zhang and Xuanyi Lv and Zhihong Deng and Rui Zhuo and Jie Dong and Qiang Wang and Xuefeng Shi and Sijie Wu and Ulf D. Kahlert and Wenjie Shi and Yefang Hu and Li Xia},
  journal = {Oncology Research},
  year = {2026},
  month = oct,
  doi = {10.32604/or.2026.089550},
  url = {https://doi.org/10.32604/or.2026.089550},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Tumor Microenvironment-Mediated Resistance in HER2-Positive Breast Cancer: Recent Advances and Therapeutic Challenges
AU  - Yutong Zhang
AU  - Xuanyi Lv
AU  - Zhihong Deng
AU  - Rui Zhuo
AU  - Jie Dong
AU  - Qiang Wang
AU  - Xuefeng Shi
AU  - Sijie Wu
AU  - Ulf D. Kahlert
AU  - Wenjie Shi
AU  - Yefang Hu
AU  - Li Xia
PY  - 2026
DA  - 2026/10/28
JO  - Oncology Research
DO  - 10.32604/or.2026.089550
UR  - https://doi.org/10.32604/or.2026.089550
AB  - Human epidermal growth factor receptor 2 (HER2)-positive breast cancer is associated with aggressive disease and poor prognosis. Despite advances in HER2-targeted therapies, resistance remains a major clinical challenge. This review focuses on the mechanisms of resistance to HER2-targeted therapies, with particular emphasis on the tumor microenvironment (TME). The TME, composed of immune cells, cancer-associated fibroblasts (CAFs), and extracellular matrix components, significantly influences therapeutic responses. Immunosuppressive cells such as tumor-associated macrophages (TAMs), regulatory T cells (Tregs), and myeloid-derived suppressor cells (MDSCs) contribute to immune evasion and therapeutic resistance. Additionally, CAFs contribute to resistance by remodeling the extracellular matrix and creating physical barriers that restrict drug delivery and immune cell infiltration. Emerging therapeutic strategies targeting the TME components show promise in overcoming resistance and improving treatment outcomes. The development of predictive biomarkers, particularly those reflecting TME components, and the integration of spatial profiling technologies will be critical in optimizing personalized treatment strategies for HER2-positive breast cancer.
SN  - 0965-0407
SN  - 1555-3906
ER  -