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Drug Target Encyclopedia Series (15) — HER3（ERBB3）

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Release Time：

2025-12-05 13:59

 

HER3 (human epidermal growth factor receptor 3, ERBB3) is a member of the ERBB receptor tyrosine kinase family, but unlike EGFR (ERBB1) or HER2 (ERBB2), HER3 has impaired kinase activity and relies on heterodimerization—especially with HER2—for signaling. This unique biology makes HER3 both a challenging and intriguing therapeutic target.

HER3 is implicated in:

• Breast cancer (particularly HER2+ and hormone receptor–positive subtypes)

• Non–small cell lung cancer (NSCLC)

• Ovarian cancer

• Gastric cancer

• Head and neck squamous cell carcinoma

Targeting HER3 in therapy:

  • Monoclonal antibodies – Patritumab deruxtecan (HER3-DXd), an ADC targeting HER3, has demonstrated promising efficacy in NSCLC and breast cancer.
  • Antibody-drug conjugates (ADCs) – Several HER3-directed ADCs are advancing in clinical pipelines with strong anti-tumor activity.
  • Bispecific antibodies – HER2/HER3 and EGFR/HER3 bispecifics are being developed to block compensatory signaling pathways.
  • RNA-based and CAR-T approaches – Emerging strategies are exploring HER3 as an immunotherapy target in solid tumors.

Challenges include:

• Limited expression in normal tissues but dynamic regulation in tumors

• Tumor heterogeneity and adaptive resistance mechanisms

• Need for predictive biomarkers to identify HER3-dependent cancers

🔬 Ongoing research is focusing on ADC optimization, bispecific combinations, and integration of HER3 blockade with checkpoint inhibitors or HER2-targeted therapies to maximize benefit.

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Drug Target Encyclopedia Series (16) —PDGFRA

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