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HER3’s Rising Role in Cancer and Therapy
- HER3, a receptor tyrosine kinase, has gained prominence in cancer biology and therapeutic development within the HER/ErbB family, despite its weak intrinsic kinase activity.
- HER3 primarily functions through ligand-induced heterodimerization to activate downstream signaling pathways crucial for cell growth, survival, and differentiation.
- Aberrant HER3 expression is linked to various cancers, impacting tumor progression and resistance to therapy, emphasizing the importance of understanding HER3 signaling intricacies.
- While early attempts to target HER3 with monoclonal antibodies were unsuccessful, next-generation agents like antibody–drug conjugates and bispecific antibodies show promise in clinical trials.
- The FDA's approval of zenocutuzumab, a HER3 × HER2 bispecific antibody, for NRG1 fusion-positive NSCLC and pancreatic cancers marks a significant advancement in HER3-targeted therapy.
- HER3's role in activating key signaling pathways and its involvement in resistance mechanisms highlight its potential as a crucial target in cancer therapy.
- Combining HER3-targeted therapies with existing inhibitors offers a strategy to overcome resistance and improve patient outcomes by co-targeting signaling pathways in cancer cells.
- Research indicates a connection between HER3 signaling and the tumor immune microenvironment, suggesting opportunities for synergistic effects with immunotherapies.
- Developing robust biomarker strategies to identify patients who will benefit from HER3-targeted therapy is crucial for personalized treatment approaches.
- Despite challenges like tumor heterogeneity and therapy resistance, ongoing research aims to expand the application of HER3-targeted therapies across various solid tumors.
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