Stemming resistance to HER-2 targeted therapy
Philippe L Bedard1, Fatima Cardoso, Martine J Piccart-Gebhart
1Department of Medical Oncology, Jules Bordet Institute, Brussels, Belgium.
Journal of Mammary Gland Biology and Neoplasia
|March 5, 2009
Summary
Resistance to HER-2 targeted therapy in breast cancer is a growing problem. Cancer stem cells (CSCs) may drive this resistance, suggesting new therapeutic strategies targeting HER-2 positive CSCs are needed.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Trastuzumab and lapatinib have improved outcomes for HER-2 positive breast cancer.
- Resistance to HER-2 targeted therapy presents a significant clinical challenge.
Purpose of the Study:
- To explore the role of the HER-2 pathway in maintaining cancer stem cells (CSCs).
- To investigate the mechanisms of resistance to HER-2 targeted therapy, focusing on CSCs.
Main Methods:
- Review of recent evidence linking HER-2 pathway to CSC maintenance.
- Analysis of known resistance mechanisms to trastuzumab, including binding site alterations, pathway activation, and epithelial-mesenchymal transition (EMT).
Main Results:
- The HER-2 pathway appears crucial for sustaining HER-2 positive CSCs.
- CSCs may be the underlying cause of resistance to HER-2 targeted therapies.
- Novel HER-2 targeted approaches show promising early clinical results.
Conclusions:
- CSCs are implicated in resistance to HER-2 targeted therapies.
- Future trials should incorporate methods to evaluate the impact of new therapies on HER-2 positive CSCs.
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