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HER3 mRNA as a predictive biomarker in anticancer therapy
1Genentech, Inc., Oncology Biomarker Development, 1 DNA Way, South San Francisco, 94080-4990, USA. amler@gene.com
Importance Of The Field:
Heterodimerization of human EGF receptor (HER) 2 and HER3, a co-receptor of HER2, plays an important and dominant role in the functionality and transformation of HER-mediated pathways. Understanding the role of HER3 in oncogenesis as well as its place as a target for anticancer therapy is an ongoing area of research. Determination of biomarkers for clinical benefit from agents targeting HER3 is an essential component of translating basic science into real-world effective anticancer therapies, with the aim of ensuring the patients most likely to benefit from such treatments can be identified.
Areas Covered In This Review:
This review focuses on the targeting of HER2 and HER3 by monoclonal antibodies and the potential for HER3 mRNA levels to predict treatment outcome in ovarian cancer.
What The Reader Will Gain:
An understanding of the value of biomarkers for clinical benefit to anticancer therapy and the current status of HER3 mRNA as a biomarker for clinical benefit of the HER2-HER3 dimerization inhibitor pertuzumab.
Take Home Message:
HER3 mRNA levels may be a biomarker for active ligand-induced HER2-HER3 signaling, with low HER3 mRNA levels correlated with clinical benefit from the HER2-HER3 dimerization inhibitor pertuzumab.
Insights
Low HER3 mRNA levels may predict patient benefit from HER2-HER3 dimerization inhibitors like pertuzumab. This finding is crucial for identifying patients likely to respond to targeted anticancer therapies.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacogenomics
Background:
- The heterodimerization of human epidermal growth factor receptor (HER) 2 and HER3 is critical for HER-mediated pathway signaling and cellular transformation.
- HER3 is an important target in oncogenesis, necessitating research into its role and therapeutic targeting.
- Identifying biomarkers for clinical benefit is essential for effective translation of HER3-targeted therapies.
Purpose of the Study:
- To review the targeting of HER2 and HER3 by monoclonal antibodies.
- To evaluate HER3 mRNA levels as a predictive biomarker for treatment outcomes in ovarian cancer.
Main Methods:
- Review of literature on HER2-HER3 targeting agents.
- Analysis of HER3 mRNA levels as a potential biomarker.
Main Results:
- HER3 mRNA levels show potential as a biomarker for predicting clinical benefit.
- Low HER3 mRNA levels correlate with positive outcomes when using the HER2-HER3 dimerization inhibitor pertuzumab.
Conclusions:
- HER3 mRNA levels may indicate active ligand-induced HER2-HER3 signaling.
- Low HER3 mRNA levels are associated with clinical benefit from pertuzumab, suggesting its utility in patient selection.
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