title: HIF inhibitors for ischemic retinopathies and cancers: options beyond anti-VEGF therapies.
abstract: Aberrant activation of the hypoxia inducible factor (HIF) pathway causing overexpression of angiogenic genes, like vascular endothelial growth factor (VEGF), is one of the underlying causes of ocular neovascularization (NV) and metastatic cancer. Consistently, along with surgical interventions, a number of anti-VEGF agents have been approved by FDA for the treatment of ocular neovascular diseases. These anti-VEGF agents, like ranibizumab/lucentis, have revolutionized the treatment in the past decade. However, substantial vision improvement is observed only in a subset of age-related macular degeneration patients receiving ranibizumab. Further, all current therapies are associated with limitations and side effects. For example, surgeries cause tissue destruction and inflammation while anti-VEGF therapies are expensive, require repeated administration, and offer temporary relief from vascular leakage. These factors impose significant cost and treatment burdens to both the patient and society. With an aging population in most western countries with a continually increasing number of patients on lifelong treatment for these retinal diseases, the focus of ocular drug development for neovascular diseases will be to improve efficacy while reducing treatment costs. Blocking the HIF pathway, a major regulator of ocular NV and cancer, offers an appealing therapeutic strategy. Therefore, this review summarizes HIF inhibitors that have been recently evaluated for the treatment of different cancers and ischemic retinopathies.
authors.affiliation: Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA.
authors.forename: Saima
authors.initials: S
authors.lastname: Subhani
authors.affiliation: Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA.
authors.forename: Divya Teja
authors.initials: DT
authors.lastname: Vavilala
authors.affiliation: Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA. mukherjim@umkc.edu.
authors.forename: Mridul
authors.initials: M
authors.lastname: Mukherji
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D018943:Anthracyclines / Q000627:therapeutic use; D001713:Biphenyl Compounds / Q000627:therapeutic use; D002301:Cardiac Glycosides / Q000627:therapeutic use; D006801:Humans; D051793:Hypoxia-Inducible Factor 1 / Q000037:antagonists & inhibitors*; D007191:Indazoles / Q000627:therapeutic use; D017705:Lignans / Q000627:therapeutic use; D008954:Models, Biological; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D015861:Retinal Neovascularization / Q000188:drug therapy*; D042442:Vascular Endothelial Growth Factors / Q000037:antagonists & inhibitors*; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D018943:Anthracyclines; D001713:Biphenyl Compounds; D002301:Cardiac Glycosides; D051793:Hypoxia-Inducible Factor 1; D007191:Indazoles; D017705:Lignans; D042442:Vascular Endothelial Growth Factors; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole
keywords: HIF inhibitors; Honokiol; Hypoxia inducible factor; Metastatic cancer; Ocular neovascularization; VEGF