• Clinical breast cancer · Nov 2010

    Review

    Targeting endocrine resistance: is there a role for mTOR inhibition?

    • Amna Sheri, Lesley-Ann Martin, and Stephen Johnston.
    • Breast Unit, Royal Marsden Hospital, 123 Old Brompton Road, London, United Kingdom. amna.sheri@icr.ac.uk
    • Clin. Breast Cancer. 2010 Nov 1; 10 Suppl 3: S79-85.

    AbstractThe phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is a critical intracellular signaling cascade that mediates both growth factor-induced proliferation and cell survival with deregulated signaling through this pathway, a feature of most cancers. Here, we review the role of the PI3K/Akt/mTOR pathway in endocrine-resistant breast cancer and discuss preclinical and clinical studies combining endocrine therapy with mTOR inhibition. Key to the success of such an approach will be a clinical trial design incorporating appropriate tumor selection and validation of biomarkers predicting benefit. Ultimately, a greater understanding of the biology and compensatory mechanisms will allow the partnering of key signal transduction inhibitors together to provide maximal "vertical" or "horizontal" blockade with further preclinical and clinical studies planned to examine possible synergistic combinations with endocrine therapy.

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