We show that treatment of Pten(i)pe−/− mice at 3 and 10 months AGI with PX-478 elicits profound antitumor effects, including the induction of apoptosis in early PIN lesions, and a decrease in the proliferation of late ones, which phenocopies the effects of combined inactivation of Pten and Hif1a in luminal cells. Here, HIF1A is linked to prostate intraepithelial neoplasia.