This project seeks to increase the anti-myeloma (MM) effects of standard or new therapies by specifically blocking the activity of insulin-like growth factors (IGFs). Our recent work has shown that IGFs, which are present in the bone marrow (BM) of MM patients, decrease the anti-MM effect of current therapies. We will therefore define new strategies to a) decrease the production of IGFs in the BM and b) block the protective effect of IGFs on MM cells against therapy. These efforts will provide the framework for use of such therapies against the IGFs/IGF-1R pathway to improve the outcome of patients with MM.