Therapeutic Targeting of MYC and HIF Networks in Cancer

The MYC oncogene is involved in many human cancers, which in general develop under limited amount of oxygen (hypoxia) requiring the activity of hypoxia inducible factors (HIFs). The interaction of MYC, which encodes a transcription factor Myc, with HIF under physiological conditions provides insights into normal cellular responses to hypoxia via cell growth arrest and anaerobic glycolysis. Many tumors contain genetic alterations, such as MYC activation, that can collaborate with HIF to confer metabolic advantages to tumor cells, which tend to exist in a hypoxic microenvironment. The collaboration of oncogenic Myc with HIF favors the conversion of glucose to lactate which could be exploited for therapeutic purposes. This article reviews the transcriptional network operative in a tumorigenic milieu and therapeutic opportunities within the Myc and HIF network of target genes.