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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
PubMed

Insights

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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