 EGFr inhibition has been shown to have down-regulatory effects on VEGF expression and angiogenesis. The combination of anti-VEGF and anti-EGFr targeting is clinically rational, and preliminarily has shown at least additive, if not synergistic effects 12, 13. Further, preclinical data has shown that constitutive activation of the AKT pathway is a mechanism of resistance to EGFr inhibitors 14. Therefore, inhibition of both EGFr and AKT pathways by panitumumab and RAD001 may create a synergistic antitumor effect. There is also rationale that RAD001 and anti-VEGF therapies may be synergistic. Preliminary results from a Phase I dose escalation study of bevacizumab in combination with RAD001 has reported a recommended Phase II dose of this combination, and has described a minor response in a colorectal cancer patient previously refractory to bevacizumab-based therapy, and over 10 months of stable disease in another colorectal cancer patient previous refractory to bevacizumab-based therapy 15. 