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Updated: Sep 13, 2025
Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
Published on: December 5, 2017
HER3 in breast cancer: molecular insights, clinical implications, and therapeutic horizons
1Department of Medical Oncology, Bower Hospital, Diyarbakır, Turkey.
Introduction:
erb-b2 receptor tyrosine kinase 3 (ERBB3/HER3) a kinase-inactive HER family receptor, significantly influences breast cancer by enhancing oncogenic signaling mainly via HER2 heterodimerization. Its role in therapy resistance marks it as a key target across subtypes, tackling a critical oncology challenge.
Areas Covered:
This review delves into HER3's molecular structure, with its ligand-binding extracellular domain and tyrosine-rich tail activating PI3K/AKT and MAPK/ERK pathways. It examines HER3's impact on tumor progression - like invasion and metastasis - and resistance to therapies such as trastuzumab, endocrine treatments, and chemotherapy across HER2- positive, hormone receptor-positive, and triple-negative subtypes, based on extensive literature. Clinically, it assesses HER3's prognostic role, with overexpression in 30-50% of cases, and therapeutic advances, notably antibody-drug conjugates (ADCs) like patritumab deruxtecan, promising in trials.
Expert Opinion:
HER3's therapeutic potential is transformative, with ADCs and combinations poised to redefine personalized care by improving survival in resistant cases. Its overexpression offers a strategic leverage point, yet inconsistent detection and adaptive resistance pose barriers. These demand innovative solutions, such as refined diagnostics and multi-target therapies. Given its demonstrated efficacy, HER3-targeted therapies, supported by novel therapeutic combinations and bioengineering innovations, are expected to become integral to routine clinical practice in the coming years, advancing precision oncology.
Insights
The erb-b2 receptor tyrosine kinase 3 (ERBB3/HER3) is crucial in breast cancer progression and therapy resistance. Targeting HER3 with antibody-drug conjugates and combinations shows promise for improved patient survival.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- The erb-b2 receptor tyrosine kinase 3 (ERBB3/HER3) is a kinase-inactive HER family receptor.
- HER3 significantly influences breast cancer by enhancing oncogenic signaling, primarily through HER2 heterodimerization.
- Its role in therapy resistance makes it a critical target across various breast cancer subtypes.
Purpose of the Study:
- To review HER3's molecular structure and its role in activating key signaling pathways (PI3K/AKT, MAPK/ERK).
- To examine HER3's impact on tumor progression, including invasion and metastasis.
- To assess HER3's role in resistance to therapies like trastuzumab, endocrine treatments, and chemotherapy across different breast cancer subtypes.
Main Methods:
- Literature review of HER3's structure, function, and clinical significance.
- Analysis of HER3's involvement in tumor progression and therapeutic resistance mechanisms.
- Evaluation of clinical data on HER3 overexpression and its prognostic value.
- Assessment of emerging HER3-targeted therapies, particularly antibody-drug conjugates (ADCs).
Main Results:
- HER3 overexpression is observed in 30-50% of breast cancer cases, correlating with a poor prognostic role.
- HER3 contributes to resistance against trastuzumab, endocrine treatments, and chemotherapy in HER2-positive, hormone receptor-positive, and triple-negative breast cancer.
- Antibody-drug conjugates (ADCs) like patritumab deruxtecan show promising results in clinical trials for HER3-targeted therapy.
Conclusions:
- HER3-targeted therapies, especially ADCs and combination treatments, hold transformative potential for personalized breast cancer care.
- Overcoming challenges like inconsistent HER3 detection and adaptive resistance requires refined diagnostics and multi-target therapeutic strategies.
- HER3-targeted therapies are expected to become integral to precision oncology, improving survival rates in resistant breast cancer cases.
