A key mediator of hypoxic signaling is hypoxia-inducible factor-1 (HIF-1), which initiates the transcription of hypoxia-response-related genes.62 Many of these genes are prometastatic and are essential for angiogenesis, tumor cell apoptosis, and growth factor/cytokine activities.63 Tumor cells that can survive in the hypoxic bone microenvironment then colonize and thrive in bones, leading to a vicious cycle of bone metastases. The gene discussed is HIF1A; the disease is neoplasm.