Abstract: In some aspects, the invention provides a method of inhibiting interaction of Six1 with Eya2 comprising contacting a cell expressing Six1 and Eya2 with an agent that inhibits binding of Six1 to Eya2 or an agent that inhibits the phostphatase activity of Eya2 on Six1. In other apsects, the invention provides a method of treating cancer in a subject comprising administering to said subject an effective amount of an agent that inhibits Six1 interaction with Eya2 or an agent that inhibits the phostphatase activity of Eya2 on Six1. In some embodiments, the invention further provides for the administration of a second cancer therapy to the patient. In still further aspects, the invention provides a method of identifying a candidate anti-cancer agent. The candidate inhibitor may be a nucleic acid, a protein, a peptide or a small molecule.