Most of these compounds affect HIF-1 target gene expression only at micromolar concentrations like PX-47829 and acriflavine21 or display distinct pharmacological profiles with primary modes of action different from direct HIF-1 inhibition that may rather explain their antitumor efficacy in preclinical cancer models, for example, topoisomerase I inhibitors30, HSP90 inhibitors31, and Pi3K/Akt/mTOR inhibitors19,32. This evidence concerns the gene MTOR and cancer.