Review

New targets for therapy in breast cancer: Mammalian target of rapamycin (mTOR) antagonists

Hetty Carraway^* and Manuel Hidalgo

• * Corresponding author: Hetty Carraway hcarraw1@jhmi.edu

Author Affiliations

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Hospital, Cancer Research Building, Baltimore, Maryland, USA

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Breast Cancer Res 2004, 6:219-224 doi:10.1186/bcr927

Published: 12 August 2004

Abstract

Mammalian target of rapamycin (mTOR) is a serine-threonine kinase member of the cellular phosphatidylinositol 3-kinase (PI3K) pathway, which is involved in multiple biologic functions such as transcriptional and translational control. mTOR is a downstream mediator in the PI3K/Akt signaling pathway and plays a critical role in cell survival. In breast cancer this pathway can be activated by membrane receptors, including the HER (or ErbB) family of growth factor receptors, the insulin-like growth factor receptor, and the estrogen receptor. There is evidence suggesting that Akt promotes breast cancer cell survival and resistance to chemotherapy, trastuzumab, and tamoxifen. Rapamycin is a specific mTOR antagonist that targets this pathway and blocks the downstream signaling elements, resulting in cell cycle arrest in the G₁ phase. Targeting the Akt/PI3K pathway with mTOR antagonists may increase the therapeutic efficacy of breast cancer therapy.