• Breast · Oct 2015

    Review

    Potential of overcoming resistance to HER2-targeted therapies through the PI3K/Akt/mTOR pathway.

    • Sharon T Wilks.
    • Cancer Care Centers of South Texas, US Oncology, San Antonio, TX 78229, USA. Electronic address: sharon.wilks@usoncology.com.
    • Breast. 2015 Oct 1; 24 (5): 548-55.

    AbstractHuman epidermal growth factor receptor 2 (HER2) overexpression occurs in up to 30% of breast cancers and is a marker of aggressive disease. While HER2-targeted therapies have improved outcomes in these tumors, resistance to these agents develops in a large proportion of patients. Determining molecular mechanisms underlying resistance might help improve outcomes for patients with HER2-positive disease by allowing development of strategies to overcome resistance. Activation of signaling pathways involving the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway might contribute to the development of resistance to HER2-targeted therapies. Several inhibitors of this pathway are under investigation in this disease setting and phase 3 data for everolimus in combination with trastuzumab and chemotherapy in trastuzumab-refractory, advanced disease are promising. In this review, molecular mechanisms underlying resistance to HER2-targeted therapies are considered and evidence for strategies to manage resistance is evaluated, including the use of inhibitors of the PI3K/Akt/mTOR pathway. Copyright © 2015 The Author. Published by Elsevier Ltd.. All rights reserved.

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