Biologic impact and clinical implication of mTOR inhibition in metastatic breast cancer



The goal of therapy for patients with metastatic breast cancer (MBC) is prolonging life and palliation of symptoms. Thus the preferred approach remains to use, at least initially, non-cytotoxic drugs. In hormone receptor-positive breast cancer the sequential use of single anti-estrogen drugs, e.g. tamoxifen, aromatase inhibitors, and many others is standard, but eventually drug resistance will lead to failure of these compounds and a switch to chemotherapy will be necessary. Reversing resistance to anti-estrogen therapy in MBC is one of the strategies to avoid and delay the use of cytotoxic compounds. The mammalian target of rapamycin (mTOR) has been recently associated with in vitro reversal of drug resistance, including tamoxifen resistance. A number of early clinical studies have confirmed the concept and, more recently, everolimus was successfully tested in a randomized controlled trial in postmenopausal patients who progressed on previous anti-estrogen therapy for MBC. This manuscript will review the biology, preclinical and clinical data including the randomized controlled trial that lead to the approval of everolimus by the US FDA.

Int J Biol Markers 2013; 28(3): 233 - 241

Article Type: REVIEW



Gustavo F. Westin, Cesar A. Perez, Emilie Wang, Stefan Glück

Article History


Financial Support: None.
Conflict of Interest Statement: None.

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  • Sylvester Comprehensive Cancer Center, University of Miami, Leonard M. Miller School of Medicine, Miami, Florida - USA
  • Florida State University College of Medicine Tallahassee, Florida - USA

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