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Analyzing Tumor and Tissue Distribution of Target Antigen Specific Therapeutic Antibody
Published on: May 16, 2020
Targeting HER3 using mono- and bispecific antibodies or alternative scaffolds
Magdalena Malm1, Fredrik Y Frejd2,3, Stefan Ståhl1
1a Division of Protein Technology, School of Biotechnology, KTH-Royal Institute of Technology, SE , Stockholm.
Abstract:
The human epidermal growth factor receptor 3 (HER3) has in recent years been recognized as a key node in the complex signaling network of many different cancers. It is implicated in de novo and acquired resistance against therapies targeting other growth factor receptors, e.g., EGFR, HER2, and it is a major activator of the PI3K/Akt signaling pathway. Consequently, HER3 has attracted substantial attention, and is today a key target for drugs in clinical development. Sophisticated protein engineering approaches have enabled the generation of a range of different affinity proteins targeting this receptor, including antibodies and alternative scaffolds that are either mono- or bispecific. Here, we describe HER3 and its role as a key tumor target, and give a comprehensive review of HER3-targeted proteins currently in development, including discussions on the opportunities and challenges of targeting this receptor.
Insights
Human epidermal growth factor receptor 3 (HER3) is a key cancer target, driving resistance to therapies and activating PI3K/Akt signaling. HER3-targeted drugs, including antibodies and bispecific proteins, are in development, presenting opportunities and challenges.
Area of Science:
- Oncology
- Molecular Biology
- Drug Development
Background:
- Human epidermal growth factor receptor 3 (HER3) is a critical component in cancer signaling networks.
- HER3 plays a significant role in both initial and acquired resistance to therapies targeting other growth factor receptors like EGFR and HER2.
- It is a primary activator of the PI3K/Akt signaling pathway, crucial for cell survival and proliferation.
Purpose of the Study:
- To review the role of HER3 as a key tumor target.
- To provide a comprehensive overview of HER3-targeted proteins currently under development.
- To discuss the potential benefits and hurdles associated with targeting HER3.
Main Methods:
- Literature review of HER3's role in cancer.
- Analysis of protein engineering strategies for HER3-targeted therapies.
- Compilation and discussion of HER3-targeted drugs in clinical development.
Main Results:
- HER3 is implicated in resistance mechanisms across various cancers.
- Diverse protein-based therapeutics targeting HER3 have been engineered.
- These include monoclonal antibodies, bispecific antibodies, and alternative protein scaffolds.
Conclusions:
- HER3 is a validated and significant target in oncology.
- Advanced protein engineering has yielded promising HER3-targeting agents.
- Further research and development are necessary to overcome challenges and realize the full therapeutic potential of targeting HER3.
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