Stemming resistance to HER-2 targeted therapy.
Although the development of trastuzumab and lapatinib has improved the outlook for women with HER-2 positive breast cancer, resistance to HER-2 targeted therapy is a growing clinical dilemma. Recent evidence indicates that the HER-2 pathway may play an important role in the maintenance of cancer stem cells (CSCs). The success of HER-2 targeted therapies may, in part, be explained by their direct activity against HER-2 positive CSCs. Our understanding of the mechanisms involved in resistance to trastuzumab, including loss or blockade of the trastuzumab binding site, activation of alternative signaling pathways, and induction of epithelial-mesenchymal transition (EMT), suggests that CSCs may be at the root of resistance of HER-2 targeted therapy. A variety of novel HER-2 targeted approaches have demonstrated promising preliminary clinical activity. Future clinical trials should involve the integration of technologies to assess the impact of novel HER-2 targeted therapies on HER-2 positive CSCs.
Bedard
Philippe L
PL
Department of Medical Oncology, Jules Bordet Institute, Brussels, Belgium.
Cardoso
Fatima
F
Piccart-Gebhart
Martine J
MJ
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017326:Clinical Trials, Phase III as Topic; D019008:Drug Resistance, Neoplasm; D006801:Humans; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases