 RAD001 Everolimus, an oral derivative of rapamycin, selectively inhibits mTOR mammalian target of rapamycin, an intracellular protein kinase implicated in the control of cellular proliferation of activated T-lymphocytes or neoplastic cells. mTOR is considered to be a downstream component of the PI3KAKTTSC pathway, a signalling module known to be heavily deregulated in many human cancers4, 5. In this context, there is an increasing body of evidence suggesting that AKT regulates mTOR activity5-7, and that the activation status of the PI3KAKT pathway may be indicative of responsiveness to rapamycins such as RAD001. Specifically, loss of PTEN or constitutivehyper-activation of AKT has been suggested to sensitize tumors to the effects of inhibition of mTOR6-8. Indeed, RAD001 preferentially inhibits the proliferation of tumor cells displaying high AKT activity and totally reverses AKT-driven prostate intraepithelial neoplasia in a mouse transgenic model7. Rapamycins also inhibit downstream signaling pathways of VEGF. The rapamycin-regulated PI3K and p70s6 pathways are known to be involved in mediating VEGFs effects on endothelial cells 9. In animal models, rapamycins modestly decrease tumor VEGF expression, and significantly blunt typical angiogenic responses to VEGF. Everolimus has been shown to inhibit tumor growth and reduce number of blood vessels in a murine melanoma model, indicating that RAD001 has direct antiangiogenic effects 10. 