From the Vascular Program, Institute for Cell Engineering; Departments of Pediatrics, Medicine, Oncology, and Radiation Oncology; and McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205
Author's disclosure of potential conflicts of interest is found at the end of this article.
Address reprint requests to Gregg L. Semenza, MD, PhD, Broadway Research Building, Suite 671, 733 North Broadway, Baltimore, MD 21205; e-mail: gsemenza{at}jhmi.edu
Overview: Hypoxia-inducible factor 1 (HIF-1) regulates the transcription of many genes involved in key aspects of cancer biology, including immortalization, maintenance of stem cell pools, cellular dedifferentiation, genetic instability, vascularization, metabolic reprogramming, autocrine growth factor signaling, invasion, metastasis, and treatment failure. In animal models, HIF-1 overexpression is associated with increased tumor growth, vascularization, and metastasis, whereas HIF-1 loss of function has the opposite effect, thus validating HIF-1 as a target. Immunohistochemical detection of HIF-1 alpha overexpression in biopsy sections is a negative prognostic factor in many cancers.
