This article is part of a series on New targets for therapy in breast cancer, edited by Stephen RD Johnston.

Review

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

Hetty Carraway and Manuel Hidalgo

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

author email corresponding author email

Breast Cancer Res 2004, 6:219-224doi: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.