Human cancers frequently display abnormalities in signaling pathways that regulate cell proliferation and survival. In breast cancer, there is an increasing recognition of the pivotal role played by the growth factor receptors-PI3K-Akt-mTOR-S6K1 pathway. The ErbB2 receptor is overproduced in approximately one-third of breast tumors, and it correlates with poor clinical prognosis [1, 2]. Breast cancer therapies targeted against ErbB2, although very specific, do not apply to all patients as some cells become resistant. It often correlates with hyperactivation of PI3K, Akt and S6K1 kinases or mutations in suppressor gene coding for PTEN phosphatase [3]. Reduced PTEN protein expression was seen in 38 % of invasive cancers and in 11 % of in situ breast cancers [4]. Moreover, estrogen receptor (ERα) activation can directly drive the PI3K-Akt pathway. Constitutive activation of Akt is associated with the resistance to either tamoxifen treatment or estrogen deprivation in hormone-dependent cancers [5]. Thus, targeting the critical downstream members of the pathways that cells remained dependent upon might be the way to overcome their resistance. Indeed, preclinical studies have shown that the mTOR antagonists can restore endocrine sensitivity in breast cancer cells [6].