['Resistance to endocrine therapy is a major impediment in breast cancer therapeutics. The Phosphatidylinositol-3-OH kinase (PI3K)/Protein kinase B (Akt/PKB) kinase signaling pathway has been implicated in altering breast cancer response to multiple therapies. How Akt modulates response is an area of significant clinical relevance.', 'We have used an in vitro model to discern the effects of robust Akt activity on breast cancer cellular response to endocrine therapies.', 'High levels of Akt activity confer resistance to the aromatase inhibitor Letrozole (Let) and the selective estrogen receptor (ER) down-regulator Fulvestrant (ICI). Akt-induced resistance is not due to failure of these endocrine agents to inhibit estrogen receptor alpha activity. Instead, resistance is characterized by altered cell cycle and apoptotic response. Cotreatment with low concentrations of the mTOR inhibitor RAD-001 and either Let or ICI restores response of the resistant cells to levels observed in the responsive cells treated with either Let or ICI as a single agent.'] Is akt-induced endocrine therapy resistance reversed by inhibition of mTOR signaling?