Abstract : This study demonstrates that Hsf1 controls development of Her2-positive cancer both at the stage of initiation, via control of the oncogene-induced senescence, and progression, via regulation of tumor angiogenesis. It also dissects the mechanism of effects of Hsf1 on tumor angiogenesis, and demonstrates that Hsf1 regulates expression of the major angiogenesis factor HIF- 1, and this regulation involves the translation regulator HuR. This program provides rationale for development of Hsf1 inhibitors that can inhibit multiple pathways in tumor initiation and progression. It also establishes a simple xenograft model that can be used for anti-Hsf1 drug testing.