Related Experiment Video
Updated: Dec 6, 2025
Quantifying Antibody-Dependent Cellular Cytotoxicity in a Tumor Spheroid Model: Application for Drug Discovery
Published on: April 26, 2024
New insights into affinity proteins for HER2-targeted therapy: Beyond trastuzumab
Vajihe Akbari1, C Perry Chou2, Daryoush Abedi3
1Department of Pharmaceutical Biotechnology, Isfahan Pharmaceutical Research Center, Faculty of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.
Abstract:
Human epidermal growth factor receptor 2 (HER2) is known as a potential target for both cancer treatment and diagnosis. One of the most interesting HER2-targeted therapeutics is an affinity protein which selectively recognizes and binds to a defined target. Trastuzumab is a monoclonal antibody which has been approved as the first affinity proteins for treatment of some HER2-positive cancers including breast cancer. Despite initial response to trastuzumab, the majority of patients with metastatic HER2-positive breast cancer still show resistance to the therapy. Recently, various anti-HER2 affinity proteins, including antibodies, antibody fragments (e.g., Fab and scFv) and other protein scaffolds (e.g., affibody and DARPin), alone or fused/conjugated with therapeutic agents (e.g., proteins, drugs and radioisotopes) have been developed to overcome the trastuzumab resistance. Here, we review these engineered affinity proteins which are either clinically approved or under evaluation. Modern technologies and future prospects for their clinical applications in cancer treatment are also discussed.
Insights
Engineered affinity proteins targeting human epidermal growth factor receptor 2 (HER2) offer new hope for patients with HER2-positive breast cancer resistant to trastuzumab therapy. These advanced therapeutics show promise for improved cancer treatment outcomes.
Area of Science:
- Oncology
- Biotechnology
- Immunotherapy
Background:
- Human epidermal growth factor receptor 2 (HER2) is a key target in cancer therapy.
- Trastuzumab, a monoclonal antibody, is an approved HER2-targeted therapy for HER2-positive cancers.
- Therapeutic resistance to trastuzumab remains a significant challenge in metastatic HER2-positive breast cancer.
Purpose of the Study:
- To review engineered affinity proteins developed to overcome trastuzumab resistance.
- To discuss the clinical applications and future prospects of these novel anti-HER2 agents.
Main Methods:
- Review of clinically approved and investigational anti-HER2 affinity proteins.
- Analysis of engineered proteins including antibodies, antibody fragments (Fab, scFv), and protein scaffolds (affibody, DARPin).
- Examination of therapeutic agents fused or conjugated with affinity proteins.
Main Results:
- Development of diverse engineered anti-HER2 affinity proteins to combat trastuzumab resistance.
- These proteins include various formats and can be combined with therapeutic payloads.
- Several agents are currently under clinical evaluation for cancer treatment.
Conclusions:
- Engineered affinity proteins represent a promising strategy to overcome trastuzumab resistance in HER2-positive cancers.
- These novel therapeutics, including antibody fragments and protein scaffolds, offer potential for improved patient outcomes.
- Advancements in technology are paving the way for expanded clinical applications in cancer therapy.
More Related Videos
08:59Looking for Driver Pathways of Acquired Resistance to Targeted Therapy: Drug Resistant Subclone Generation and Sensitivity Restoring by Gene Knock-down
Published on: December 11, 2017
08:28Validated Immunochemical Assay for Comprehensive Determination of the Human Epidermal Growth Factor Receptor 2 Released from and Bound to Cells
Published on: May 9, 2025
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
02:38Mitogens and the Cell Cycle
01:27Tumor Immunotherapy