title: Hypoxia inducible factor in hepatocellular carcinoma: A therapeutic target.
abstract: Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed and deadly cancers worldwide; its incidence has been rising in the United States due to the increase in hepatitis C associated cirrhosis and the growing epidemic of obesity. There have been no effective therapeutic options in the advanced disease setting beyond sorafenib, a multi-targeted tyrosine kinase inhibitor that showed significant survival benefit. Because of this, there is an urgent need to search for novel pathways in sorafenib experienced patients. This review will focus on the role of hypoxia and hypoxia-inducible factor alpha (HIF-1α) in cancer development, specifically in HCC. We will discuss the biology of HIF-1α, the pathways with which it interacts, and the function of HIF-1α in HCC. Furthermore, we will review studies highlighting the relevance of HIF-1α in the clinical setting, as well as the pre-clinical data supporting its further investigation. Finally, we will conclude with a discussion of the potential role of a HIF-1α mRNA antagonist for the treatment of HCC, and hypothesize the ways in which such an inhibitor may be best utilized in the management of advanced HCC. Hypoxia plays a significant role in the development of HCC. HIF-1α is a key transcription factor involved in the hypoxic response of cancer cells. It activates transcription of genes responsible for angiogenesis, glucose metabolism, proliferation, invasion and metastasis in HCC. Its involvement in multiple, essential tumor pathways makes it an attractive potential therapeutic target in HCC.
authors.affiliation: Daniel Lin, Fellow Hematology and Medical Oncology Program, NYU School of Medicine, Perlmutter Cancer Center, NYU Langone Medical Center, Division of Hematology and Oncology, New York, NY 10016, United States.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lin
authors.affiliation: Daniel Lin, Fellow Hematology and Medical Oncology Program, NYU School of Medicine, Perlmutter Cancer Center, NYU Langone Medical Center, Division of Hematology and Oncology, New York, NY 10016, United States.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015687:Cell Hypoxia; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy; D015398:Signal Transduction / Q000187:drug effects; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit
keywords: Hepatocellular carcinoma; Hypoxia; Hypoxia-inducible factor alpha; Vascular endothelial growth factor