Our recent studies have shown that the growth of myeloma cells can be triggered by multiple kinase molecules. These diverse targets can be simultaneously blocked with inhibitors of hsp90, a protein which facilitates the function of many such important kinases, or with multi-targeted kinase inhibitors, i.e. inhibitors which can simultaneously block the active portion of many different kinases. We have observed that hsp90 inhibitors and multi-targeted kinase inhibitors can be safely administered in animal models of myeloma and achieve anti-tumor responses. In this project, we will define the role of these agents administered in combination treatments with other promising investigational anti-myeloma treatments, aiming at enhancing their anti-myeloma activity, with the ultimate goal of improving the outcome of patients with myeloma.