 HIF-1 is a common mediator of hypoxic and non-hypoxic pathways that affects a transcriptional program leading to survival, angiogenesis, migration and invasion of cancer cells. We have demonstrated that chronic administration of topotecan inhibits HIF-1alpha expression, angiogenesis and tumor growth in human xenografts. Notably, the mechanism by which topotecan inhibits HIF-1alpha protein expression is independent of replication-mediated DNA damage, suggested a mechanism of action distinct from its cytotoxic effects. 