Hypoxia inducible factor pathway inhibitors as anticancer therapeutics

Papers of special note have been highlighted as: ▪▪ of considerable interest

References

• 1  VaupelP, Mayer A. Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev.26(2),225–239 (2007).
  Medline CASGoogle Scholar
• 2  Cairns RA, Kalliomaki T, Hill RP. Acute (cyclic) hypoxia enhances spontaneous metastasis of KHT murine tumors. Cancer Res.61(24),8903–8908 (2001).
  Medline CASGoogle Scholar
• 3  Matsumoto S. Imaging cycling tumor hypoxia. Cancer Res.70(24),10019–10023 (2010).
  Medline CASGoogle Scholar
• 4  Belozerov VE, Van Meir EG. Inhibition of hypoxia-inducible factor-1 signaling. Curr. Opin. Investig. Drugs7(12),1067–1076 (2006).
  Medline CASGoogle Scholar
• 5  Wilson W, Hay M. Targeting hypoxia in cancer therapy. Nat. Rev. Cancer11(6),393–410 (2011).
  Medline CASGoogle Scholar
• 6  Brown JM, Wilson WR. Exploiting tumor hypoxia in cancer treatment. Nat. Rev. Cancer4,437–447 (2004).
  Medline CASGoogle Scholar
• 7  Graeber TG, Osmanian C, Jacks T et al. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumors. Nature379(6560),88–91 (1996).▪▪ First study to show that hypoxia selects for tumor cells with mutations in the p53 gene that prevent hypoxia-induced apoptosis.
  Medline CASGoogle Scholar
• 8  Subarsky P, Hill RP. The hypoxic tumor microenvironment and metastatic progression. Clin. Exp. Metastasis20(3),237–250 (2003).
  Medline CASGoogle Scholar
• 9  Wang GL, Semenza GL. Purification and characterization of hypoxia-inducible factor 1. J. Biol. Chem.270(3),1230–1237 (1995).
  Medline CASGoogle Scholar
• 10  Wang GL, Jiang BH, Rue EA, Semenza GL. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O₂ tension. Proc. Natl Acad. Sci. USA92(12),5510–5514 (1995).▪▪ Reports the original cloning of hypoxia inducible factor-1α.
  Medline CASGoogle Scholar
• 11  Berra E, Benizri E, Ginouves A, Volmat V, Roux D, Pouyssegur J. HIF prolyl-hydroxylase 2 is the key oxygen sensor setting low steady-state levels of HIF-1alpha in normoxia. EMBO J.22(16),4082–4090 (2003).
  Medline CASGoogle Scholar
• 12  Hirsila M, Koivunen P, Gunzler V, Kivirikko KI, Myllyharju J. Characterization of the human prolyl 4-hydroxylases that modify the hypoxia-inducible factor. J. Biol. Chem.278(33),30772–30780 (2003).
  MedlineGoogle Scholar
• 13  Maxwell PH, Wiesener MS, Chang GW et al. The tumor suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature399(6733),271–275 (1999).
  Medline CASGoogle Scholar
• 14  Ivan M, Kondo K, Yang HF et al. HIF alpha targeted for VHL-mediated destruction by proline hydroxylation: implications for O2 sensing. Science292(5516),464–468 (2001).▪▪ Along with [13], describes the discovery of VHL as the substrate-recognition unit of the E3 ubiquitin ligase responsible for oxygen-dependent hypoxia inducible factor-α degradation.
  Medline CASGoogle Scholar
• 15  Jeong JW, Bae MK, Ahn MY et al. Regulation and destabilization of HIF-1α by ARD1-mediated acetylation. Cell111(5),709–720 (2002).
  Medline CASGoogle Scholar
• 16  Wenger RH, Stiehl DP, Camenisch G. Integration of oxygen signaling at the consensus HRE. Sci. STKE2005(306),re12 (2005).
  MedlineGoogle Scholar
• 17  Kimura H, Weisz A, Ogura T et al. Identification of hypoxia-inducible factor 1 ancillary sequence and its function in vascular endothelial growth factor gene induction by hypoxia and nitric oxide. J. Biol. Chem.276(3),2292–2298 (2001).
  Medline CASGoogle Scholar
• 18  Fath DM, Kong X, Liang D et al. Histone deacetylase inhibitors repress the transactivation potential of hypoxia-inducible factors independently of direct acetylation of HIF-α. J. Biol. Chem.281(19),13612–13619 (2006).
  Medline CASGoogle Scholar
• 19  Dayan F, Roux D, Brahimi-Horn MC, Pouyssegur J, Mazure NM. The oxygen sensor factor-inhibiting hypoxia-inducible factor-1 controls expression of distinct genes through the bifunctional transcriptional character of hypoxia-inducible factor-1α. Cancer Res.66(7),3688–3698 (2006).
  Medline CASGoogle Scholar
• 20  Kaelin WG Jr, Ratcliffe PJ. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol. Cell30(4),393–402 (2008).
  Medline CASGoogle Scholar
• 21  Kaelin WG Jr. ROS: really involved in oxygen sensing. Cell Metab.1(6),357–358 (2005).
  Medline CASGoogle Scholar
• 22  Czibik G. Complex role of the HIF system in cardiovascular biology. J. Mol. Med.88(11),1101–1111 (2010).
  Medline CASGoogle Scholar
• 23  Majmundar AJ, Wong WJ, Simon MC. Hypoxia-inducible factors and the response to hypoxic stress. Mol. Cell40(2),294–309 (2010).
  Medline CASGoogle Scholar
• 24  Zhao S, Lin Y, Xu W et al. Glioma-derived mutations in IDH1 dominantly inhibit IDH1 catalytic activity and induce HIF-1 alpha. Science324(5924),261–265 (2009).
  Medline CASGoogle Scholar
• 25  Dang L, White DW, Gross S et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature462(7274),U739–U752 (2009).
  Medline CASGoogle Scholar
• 26  Koivunen P, Lee S, Duncan CG et al. Transformation by the (R)-enantiomer of 2-hydroxyglutarate linked to EGLN activation. Nature483(7390),U485–U144 (2012).▪▪ Report showing that 2-hydroxyglutarate produced in IDH mutant tumor cells activates prolyl hydroxylase and destabilizes hypoxia inducible factor.
  Google Scholar
• 27  Bardos J, Ashcroft M. Negative and positive regulation of HIF-1: a complex network. Biochim. Biophys. Acta25(2),107–120 (2005).
  Google Scholar
• 28  Déry M-A, Michaud MD, Richard DE. Hypoxia-inducible factor 1: regulation by hypoxic and non-hypoxic activators. Int. J. Biochem. Cell. Biol.37(3),535–540 (2005).
  Medline CASGoogle Scholar
• 29  Flügel D, Görlach A, Michiels C, Kietzmann T. Glycogen synthase kinase 3 phosphorylates hypoxia-inducible factor 1α and mediates its destabilization in a VHL-independent manner. Mol. Cell. Biochem.27(9),3253–3265 (2007).
  CASGoogle Scholar
• 30  Mottet D, Dumont V, Deccache Y et al. Regulation of hypoxia-inducible factor-1α protein level during hypoxic conditions by the phosphatidylinositol 3-kinase/Akt/glycogen synthase kinase 3β pathway in HepG2 cells. J. Biol. Chem.278(33),31277–31285 (2003).
  Medline CASGoogle Scholar
• 31  Flügel D, Görlach A, Kietzmann T. GSK-3β regulates cell growth, migration, and angiogenesis via Fbw7 and USP28-dependent degradation of HIF-1α. Blood119(5),1292–1301 (2012).
  Medline CASGoogle Scholar
• 32  Xu D, Yao Y, Lu L, Costa M, Dai W. Plk3 functions as an essential component of the hypoxia regulatory pathway by direct phosphorylation of HIF-1α. J. Biol. Chem.285(50),38944–38950 (2010).
  Medline CASGoogle Scholar
• 33  Cam H, Easton JB, High A, Houghton PJ. mTORC1 signaling under hypoxic conditions is controlled by ATM-dependent phosphorylation of HIF-1α. Mol. Cell40(4),509–520 (2010).
  Medline CASGoogle Scholar
• 34  Minet E, Arnould T, Michel G et al. ERK activation upon hypoxia: involvement in HIF-1 activation. FEBS Lett.468(1),53–58 (2000).
  Medline CASGoogle Scholar
• 35  Gradin K, Takasaki C, Fujii-Kuriyama Y, Sogawa K. The transcriptional activation function of the HIF-like factor requires phosphorylation at a conserved threonine. J. Biol. Chem.277(26),23508–23514 (2002).
  Medline CASGoogle Scholar
• 36  Mottet D, Ruys SPD, Demazy C, Raes M, Michiels C. Role for casein kinase 2 in the regulation of HIF-1 activity. Int J. Cancer117(5),764–774 (2005).
  Medline CASGoogle Scholar
• 37  Richard DE, Berra E, Gothié E, Roux D, Pouysségur J. p42/p44 mitogen-activated protein kinases phosphorylate hypoxia-inducible factor 1α (HIF-1α) and enhance the transcriptional activity of HIF-1. J. Biol. Chem.274(46),32631–32637 (1999).
  Medline CASGoogle Scholar
• 38  Mylonis I, Chachami G, Samiotaki M et al. Identification of MAPK phosphorylation sites and their role in the localization and activity of hypoxia-inducible factor-1α. J. Biol. Chem.281(44),33095–33106 (2006).
  Medline CASGoogle Scholar
• 39  Kalousi A, Mylonis I, Politou AS, Chachami G, Paraskeva E, Simos G. Casein kinase 1 regulates human hypoxia-inducible factor HIF-1. J. Cell Sci.123(17),2976–2986 (2010).
  Medline CASGoogle Scholar
• 40  Van De Sluis B, Mao X, Zhai Y et al. COMMD1 disrupts HIF-1alpha/beta dimerization and inhibits human tumor cell invasion. J. Clin. Invest.120(6),2119–2130 (2010).
  Medline CASGoogle Scholar
• 41  Cho H, Ahn D-R, Park H, Yang EG. Modulation of p300 binding by posttranslational modifications of the C-terminal activation domain of hypoxia-inducible factor-1α. FEBS Lett.581(8),1542–1548 (2007).
  Medline CASGoogle Scholar
• 42  Huang LE, Bunn HF. Hypoxia-inducible factor and its biomedical relevance. J. Biol. Chem.278(22),19575–19578 (2003).
  Medline CASGoogle Scholar
• 43  Hu CJ, Wang LY, Chodosh LA, Keith B, Simon MC. Differential roles of hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha in hypoxic gene regulation. Mol. Cell. Biochem.23(24),9361–9374 (2003).
  CASGoogle Scholar
• 44  Raval RR, Lau KW, Tran MGB et al. Contrasting properties of HIF-1 and HIF-2 in Von Hippel-Lindau-associated renal cell carcinoma. Mol. Cell. Biol.25(13),5675–5686 (2005).
  Medline CASGoogle Scholar
• 45  Bertout JA, Patel SA, Simon MC. The impact of O₂ availability on human cancer. Nat. Rev. Cancer8(12),967–975 (2008).
  Medline CASGoogle Scholar
• 46  Gordan JD, Lal P, Dondeti VR et al. HIF-alpha effects on c-Myc distinguish two subtypes of sporadic VHL-deficient clear cell renal carcinoma. Cancer Cell14(6),435–446 (2008).
  Medline CASGoogle Scholar
• 47  Xu J, Wang B, Xu Y et al. Epigenetic regulation of HIF-1 alpha in renal cancer cells involves HIF-1 alpha/2 alpha binding to a reverse hypoxia-response element. Oncogene31(8),1065–1072 (2012).
  Medline CASGoogle Scholar
• 48  Giatromanolaki A, Koukourakis MI, Sivridis E et al. Relation of hypoxia inducible factor 1 alpha and 2 alpha in operable non-small cell lung cancer to angiogenic/molecular profile of tumors and survival. Br. J. Cancer85(6),881–890 (2001).
  Medline CASGoogle Scholar
• 49  Franovic A, Holterman CE, Payette J, Lee S. Human cancers converge at the HIF-2α oncogenic axis. Proc. Natl Acad. Sci. USA106(50),21306–21311 (2009).
  Medline CASGoogle Scholar
• 50  Biswas S, Troy H, Leek R et al. Effects of HIF-1alpha and HIF-2alpha on growth and metabolism of clear-cell renal cancer 786-0 xenografts. J. Oncol.2010,757908 (2010).
  MedlineGoogle Scholar
• 51  Sowter HM, Raval RR, Moore JW, Ratcliffe PJ, Harris AL. Predominant role of hypoxia-inducible transcription factor (HIF)-1alpha versus HIF-2alpha in regulation of the transcriptional response to hypoxia. Cancer Res.63(19),6130–6134 (2003).
  Medline CASGoogle Scholar
• 52  Aprelikova O, Wood M, Tackett S, Chandramouli GV, Barrett JC. Role of ETS transcription factors in the hypoxia-inducible factor-2 target gene selection. Cancer Res.66(11),5641–5647 (2006).
  Medline CASGoogle Scholar
• 53  Lim JH, Lee YM, Chun YS, Chen J, Kim JE, Park JW. Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1 alpha. Mol. Cell38(6),864–878 (2010).
  Medline CASGoogle Scholar
• 54  Dioum EM, Chen R, Alexander MS et al. Regulation of hypoxia-inducible factor 2 alpha signaling by the stress-responsive deacetylase sirtuin 1. Science324(5932),1289–1293 (2009).
  Medline CASGoogle Scholar
• 55  Gordan JD, Bertout JA, Hu CJ, Diehl JA, Simon MC. HIF-2 alpha promotes hypoxic cell proliferation by enhancing c-Myc transcriptional activity. Cancer Cell11(4),335–347 (2007).
  Medline CASGoogle Scholar
• 56  Moeller BJ, Dreher MR, Rabbani ZN et al. Pleiotropic effects of HIF-1 blockade on tumor radiosensitivity. Cancer Cell8(2),99–110 (2005).
  Medline CASGoogle Scholar
• 57  An WG, Kanekal M, Simon MC, Maltepe E, Blagosklonny MV, Neckers LM. Stabilization of wild-type p53 by hypoxia-inducible factor 1 alpha. Nature392(6674),405–408 (1998).
  Medline CASGoogle Scholar
• 58  Bertout JA, Majmundar AJ, Gordan JD et al. HIF2 alpha inhibition promotes p53 pathway activity, tumor cell death, and radiation responses. Proc. Natl Acad. Sci. USA106(34),14391–14396 (2009).
  Medline CASGoogle Scholar
• 59  Hadjipanayis CG, Van Meir EG. Tumor initiating cells in malignant gliomas: biology and implications for therapy. J. Mol. Med.87(4),363–374 (2009).
  MedlineGoogle Scholar
• 60  Heddleston JM, Li Z, Lathia JD, Bao S, Hjelmeland AB, Rich JN. Hypoxia inducible factors in cancer stem cells. Br. J. Cancer102(5),789–795 (2010).
  Medline CASGoogle Scholar
• 61  Soeda A, Park M, Lee D et al. Hypoxia promotes expansion of the CD133-positive glioma stem cells through activation of HIF-1 alpha. Oncogene28(45),3949–3959 (2009).
  Medline CASGoogle Scholar
• 62  Li Z, Bao S, Wu Q et al. Hypoxia-inducible factors regulate tumorigenic capacity of glioma stem cells. Cancer Cell15(6),501–513 (2009).
  Medline CASGoogle Scholar
• 63  Pietras A, Hansford LM, Johnsson AS et al. HIF-2 alpha maintains an undifferentiated state in neural crest-like human neuroblastoma tumor-initiating cells. Proc. Natl Acad. Sci. USA106(39),16805–16810 (2009).
  Medline CASGoogle Scholar
• 64  Gustafsson MV, Zheng XW, Pereira T et al. Hypoxia requires notch signaling to maintain the undifferentiated cell state. Dev. Cell9(5),617–628 (2005).
  Medline CASGoogle Scholar
• 65  Covello KL, Kehler J, Yu HW et al. HIF-2 alpha regulates Oct-4: effects of hypoxia on stem cell function, embryonic development, and tumor growth. Genes Dev.20(5),557–570 (2006).
  Medline CASGoogle Scholar
• 66  Moreno-Manzano V, Rodriguez-Jimenez FJ, Acena-Bonilla JL et al. FM19G11, a new hypoxia-inducible factor (HIF) modulator, affects stem cell differentiation status. J. Biol Chem.285(2),1333–1342 (2010).
  Medline CASGoogle Scholar
• 67  Avilion AA, Nicolis SK, Pevny LH, Perez L, Vivian N, Lovell-Badge R. Multipotent cell lineages in early mouse development depend on SOX2 function. Genes Dev.17(1),126–140 (2003).
  Medline CASGoogle Scholar
• 68  Takahashi K, Tanabe K, Ohnuki M et al. Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell131(5),861–872 (2007).
  Medline CASGoogle Scholar
• 69  Ortiz-Barahona A, Villar D, Pescador N, Amigo J, del Peso L. Genome-wide identification of hypoxia-inducible factor binding sites and target genes by a probabilistic model integrating transcription-profiling data and in silico binding site prediction. Nucleic Acids Res.38(7),2332–2345 (2010).
  Medline CASGoogle Scholar
• 70  Benita Y, Kikuchi H, Smith AD, Zhang MQ, Chung DC, Xavier RJ. An integrative genomics approach identifies hypoxia inducible factor-1 (HIF-1)-target genes that form the core response to hypoxia. Nucleic Acids Res.37(14),4587–4602 (2009).
  Medline CASGoogle Scholar
• 71  Tanimoto K, Tsuchihara K, Kanai A et al. Genome-wide identification and annotation of HIF-1α binding sites in two cell lines using massively parallel sequencing. HUGO J.4(1–4),35–48 (2010).
  MedlineGoogle Scholar
• 72  Schödel J, Oikonomopoulos S, Ragoussis J, Pugh CW, Ratcliffe PJ, Mole DR. High-resolution genome-wide mapping of HIF-binding sites by ChIP-seq. Blood117(23),e207–e217 (2011).
  Medline CASGoogle Scholar
• 73  Mole DR, Blancher C, Copley RR et al. Genome-wide association of hypoxia-inducible factor (HIF)-1α and HIF-2α DNA binding with expression profiling of hypoxia-inducible transcripts. J. Biol. Chem.284(25),16767–16775 (2009).
  Medline CASGoogle Scholar
• 74  Simon MP, Tournaire R, Pouyssegur J. The angiopoietin-2 gene of endothelial cells is up-regulated in hypoxia by a HIF binding site located in its first intron and by the central factors GATA-2 and Ets-1. J. Cell Physiol.217(3),809–818 (2008).
  Medline CASGoogle Scholar
• 75  Pennacchietti S, Michieli P, Galluzzo M, Mazzone M, Giordano S, Comoglio PM. Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell3(4),347–361 (2003).
  MedlineGoogle Scholar
• 76  Lofstedt T, Jogi A, Sigvardsson M et al. Induction of ID2 expression by hypoxia-inducible factor-1: a role in dedifferentiation of hypoxic neuroblastoma cells. J. Biol. Chem.279(38),39223–39231 (2004).
  MedlineGoogle Scholar
• 77  Grosfeld A, André J, Hauguel-De Mouzon S, Berra E, Pouysségur J, Guerre-Millo M. Hypoxia-inducible factor 1 transactivates the human leptin gene promoter. J. Biol. Chem.277(45),42953–42957 (2002).
  Medline CASGoogle Scholar
• 78  Melillo G, Musso T, Sica A, Taylor LS, Cox GW, Varesio L. A hypoxia-responsive element mediates a novel pathway of activation of the inducible nitric oxide synthase promoter. J. Exp. Med.182(6),1683–1693 (1995).
  Medline CASGoogle Scholar
• 79  Huang Y, Hickey RP, Yeh JL et al. Cardiac myocyte-specific HIF-1α deletion alters vascularization, energy availability, calcium flux, and contractility in the normoxic heart. FASEB J.18(10),1138–1140 (2004).
  Medline CASGoogle Scholar
• 80  Han Z-B, Ren H, Zhao H et al. Hypoxia-inducible factor (HIF)-1α directly enhances the transcriptional activity of stem cell factor (SCF) in response to hypoxia and epidermal growth factor (EGF). Carcinogenesis29(10),1853–1861 (2008).
  Medline CASGoogle Scholar
• 81  Ceradini DJ, Kulkarni AR, Tepper OM et al. Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1. Nat. Med.10(8),858–864 (2004).
  Medline CASGoogle Scholar
• 82  Levy AP, Levy NS, Wegner S, Goldberg MA. Transcriptional regulation of the rat vascular endothelial growth factor gene by hypoxia. J. Biol. Chem.270(22),13333–13340 (1995).
  Medline CASGoogle Scholar
• 83  Comerford KM, Wallace TJ, Karhausen J, Louis NA, Montalto MC, Colgan SP. Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance (MDR1) gene. Cancer Res.62(12),3387–3394 (2002).
  Medline CASGoogle Scholar
• 84  Semenza GL, Nejfelt MK, Chi SM, Antonarakis SE. Hypoxia-inducible nuclear factors bind to an enhancer element located 3´ to the human erythropoietin gene. Proc. Natl Acad. Sci. USA88(13),5680–5684 (1991).
  Medline CASGoogle Scholar
• 85  Miyazaki K, Kawamoto T, Tanimoto K, Nishiyama M, Honda H, Kato Y. Identification of functional hypoxia response elements in the promoter region of the DEC1 and DEC2 genes. J. Biol. Chem.277(49),47014–47021 (2002).
  Medline CASGoogle Scholar
• 86  Koshiji M, To KKW, Hammer S et al. HIF-1α induces genetic instability by transcriptionally downregulating MutSα expression. Mol. Cell17(6),793–803 (2005).
  Medline CASGoogle Scholar
• 87  Chen C, Pore N, Behrooz A, Ismail-Beigi F, Maity A. Regulation of glut1 mRNA by hypoxia-inducible factor-1: interaction between H-ras and hypoxia. J. Biol. Chem.276(12),9519–9525 (2001).
  Medline CASGoogle Scholar
• 88  Yoon DY, Buchler P, Saarikoski ST, Hines OJ, Reber HA, Hankinson O. Identification of genes differentially induced by hypoxia in pancreatic cancer cells. Biochem. Biophys. Res. Commun.288(4),882–886 (2001).
  Medline CASGoogle Scholar
• 89  Mathupala SP, Rempel A, Pedersen PL. Glucose catabolism in cancer cells: identification and characterization of a marked activation response of the type II hexokinase gene to hypoxic conditions. J. Biol. Chem.276(46),43407–43412 (2001).
  Medline CASGoogle Scholar
• 90  Semenza GL, Jiang B-H, Leung SW et al. Hypoxia response elements in the aldolase A, enolase 1, and lactate dehydrogenase A gene promoters contain essential binding sites for hypoxia-inducible factor 1. J. Biol. Chem.271(51),32529–32537 (1996).
  Medline CASGoogle Scholar
• 91  Sonveaux P, Copetti T, De Saedeleer CJ et al. Targeting the lactate transporter MCT1 in endothelial cells inhibits lactate-induced HIF-1 activation and tumor angiogenesis. PLoS ONE7(3),e33418 (2012).
  Medline CASGoogle Scholar
• 92  Semenza GL, Roth PH, Fang HM, Wang GL. Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. J. Biol. Chem.269(38),23757–23763 (1994).
  Medline CASGoogle Scholar
• 93  Nishi H, Nakada T, Kyo S, Inoue M, Shay JW, Isaka K. Hypoxia-inducible factor 1 mediates upregulation of telomerase (hTERT). Mol. Cell. Biol.24(13),6076–6083 (2004).
  Medline CASGoogle Scholar
• 94  Synnestvedt K, Furuta GT, Comerford KM et al. Ecto-5´-nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia. J. Clin. Invest.110(7),993–1002 (2002).
  Medline CASGoogle Scholar
• 95  Huang Y, Hickey RP, Yeh JL et al. Cardiac myocyte-specific HIF-1alpha deletion alters vascularization, energy availability, calcium flux, and contractility in the normoxic heart. FASEB J.18(10),1138–1140 (2004).
  Medline CASGoogle Scholar
• 96  Krishnamachary B, Berg-Dixon S, Kelly B et al. Regulation of colon carcinoma cell invasion by hypoxia-inducible factor 1. Cancer Res.63(5),1138–1143 (2003).
  Medline CASGoogle Scholar
• 97  Ben-Yosef Y, Lahat N, Shapiro S, Bitterman H, Miller A. Regulation of endothelial matrix metalloproteinase-2 by hypoxia/reoxygenation. Circ. Res.90(7),784–791 (2002).
  Medline CASGoogle Scholar
• 98  Petrella BL, Lohi J, Brinckerhoff CE. Identification of membrane type-1 matrix metalloproteinase as a target of hypoxia-inducible factor-2 alpha in von Hippel-Lindau renal cell carcinoma. Oncogene24(6),1043–1052 (2005).
  Medline CASGoogle Scholar
• 99  Staller P, Sulitkova J, Lisztwan J, Moch H, Oakeley EJ, Krek W. Chemokine receptor CXCR4 downregulated by von Hippel-Lindau tumor suppressor pVHL. Nature425,307–311 (2003).
  Medline CASGoogle Scholar
• 100  Erler JT, Bennewith KL, Nicolau M et al. Lysyl oxidase is essential for hypoxia-induced metastasis. Nature440(7088),1222–1226 (2006).
  Medline CASGoogle Scholar
• 101  Yang MH, Wu KJ. TWIST activation by hypoxia inducible factor-1 (HIF-1): implications in metastasis and development. Cell Cycle7(14),2090–2096 (2008).
  Medline CASGoogle Scholar
• 102  Wykoff CC, Beasley NJP, Watson PH et al. Hypoxia-inducible expression of tumor-associated carbonic anhydrases. Cancer Res.60(24),7075–7083 (2000).
  Medline CASGoogle Scholar
• 103  Koshiji M, Kageyama Y, Pete EA, Horikawa I, Barrett JC, Huang LE. HIF-1[alpha] induces cell cycle arrest by functionally counteracting Myc. EMBO J.23(9),1949–1956 (2004).
  Medline CASGoogle Scholar
• 104  Feldser D, Agani F, Iyer NV, Pak B, Ferreira G, Semenza GL. Reciprocal positive regulation of hypoxia-inducible factor 1α and insulin-like growth factor 2. Cancer Res.59(16),3915–3918 (1999).
  Medline CASGoogle Scholar
• 105  Krishnamurthy P, Ross DD, Nakanishi T et al. The stem cell marker Bcrp/ABCG2 enhances hypoxic cell survival through interactions with heme. J. Biol. Chem.279(23),24218–24225 (2004).
  Medline CASGoogle Scholar
• 106  Beyer S, Kristensen MM, Jensen KS, Johansen JV, Staller P. The histone demethylases JMJD1A and JMJD2B are transcriptional targets of hypoxia-inducible factor HIF. J. Biol. Chem.283(52),36542–36552 (2008).
  Medline CASGoogle Scholar
• 107  Mathieu J, Zhang Z, Zhou W et al. HIF induces human embryonic stem cell markers in cancer cells. Cancer Res.71(13),4640–4652 (2011).
  Medline CASGoogle Scholar
• 108  Semenza GL. Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene29,625–634 (2009).
  MedlineGoogle Scholar
• 109  Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J. Clin. Oncol.23(5),1011–1027 (2005).
  Medline CASGoogle Scholar
• 110  Coultas L, Chawengsaksophak K, Rossant J. Endothelial cells and VEGF in vascular development. Nature438(7070),937–945 (2005).
  Medline CASGoogle Scholar
• 111  Liao D, Johnson R. Hypoxia. A key regulator of angiogenesis in cancer. Cancer Metastasis Rev.26(2),281–290 (2007).
  Medline CASGoogle Scholar
• 112  Jensen R, Ragel B, Whang K, Gillespie D. Inhibition of hypoxia inducible factor-1α (HIF-1α) decreases vascular endothelial growth factor (VEGF) secretion and tumor growth in malignant gliomas. J. Neurooncol.78(3),233–247 (2006).
  Medline CASGoogle Scholar
• 113  Kim J-W, Gao P, Dang C. Effects of hypoxia on tumor metabolism. Cancer Metastasis Rev.26(2),291–298 (2007).
  MedlineGoogle Scholar
• 114  Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell120(4),483–495 (2005).
  Medline CASGoogle Scholar
• 115  Chiche J, Brahimi-Horn MC, Pouyssegur J. Tumor hypoxia induces a metabolic shift causing acidosis: a common feature in cancer. J. Cell. Mol. Med.14(4),771–794 (2010).
  Medline CASGoogle Scholar
• 116  Potter C, Harris AL. Hypoxia inducible carbonic anhydrase IX, marker of tumor hypoxia, survival pathway and therapy target. Cell Cycle3(3),159–162 (2004).
  Google Scholar
• 117  Moeller BJ, Cao Y, Li CY, Dewhirst MW. Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: role of reoxygenation, free radicals, and stress granules. Cancer Cell5(5),429–441 (2004).
  Medline CASGoogle Scholar
• 118  Moeller B, Richardson R, Dewhirst M. Hypoxia and radiotherapy: opportunities for improved outcomes in cancer treatment. Cancer Metastasis Rev.26(2),241–248 (2007).
  Medline CASGoogle Scholar
• 119  Chandel NS, Mcclintock DS, Feliciano CE et al. Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1α during hypoxia. J. Biol. Chem.275(33),25130–25138 (2000).
  Medline CASGoogle Scholar
• 120  Jung SN, Yang WK, Kim J et al. Reactive oxygen species stabilize hypoxia-inducible factor-1 alpha protein and stimulate transcriptional activity via AMP-activated protein kinase in DU145 human prostate cancer cells. Carcinogenesis29(4),713–721 (2008).
  Medline CASGoogle Scholar
• 121  Brown LM, Cowen RL, Debray C et al. Reversing hypoxic cell chemoresistance in vitro using genetic and small molecule approaches targeting hypoxia inducible factor-1. Mol. Pharmacol.69(2),411–418 (2006).
  Medline CASGoogle Scholar
• 122  Yang DI, Chen SD, Yang YT, Ju TC, Xu JM, Hsu CY. Carbamoylating chemoresistance induced by cobalt pretreatment in C6 glioma cells: putative roles of hypoxia-inducible factor-1. Br. J. Pharmacol.141(6),988–996 (2004).
  Medline CASGoogle Scholar
• 123  Liu L, Ning X, Sun L et al. Hypoxia-inducible factor-1α contributes to hypoxia-induced chemoresistance in gastric cancer. Cancer Sci.99(1),121–128 (2008).
  Medline CASGoogle Scholar
• 124  Sasabe E, Zhou X, Li D, Oku N, Yamamoto T, Osaki T. The involvement of hypoxia-inducible factor-1α in the susceptibility to γ-rays and chemotherapeutic drugs of oral squamous cell carcinoma cells. Int. J. Cancer120(2),268–277 (2007).
  Medline CASGoogle Scholar
• 125  Rohwer N, Cramer T. Hypoxia-mediated drug resistance: novel insights on the functional interaction of HIFs and cell death pathways. Drug Resist. Updat.14(3),191–201 (2011).
  Medline CASGoogle Scholar
• 126  Comerford KM, Wallace TJ, Karhausen JR, Louis NA, Montalto MC, Colgan SP. Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance (MDR1) gene. Cancer Res.62(12),3387–3394 (2002).
  Medline CASGoogle Scholar
• 127  Seagroves TN. The complexity of the HIF-1-dependent hypoxic response in breast cancer presents multiple avenues for therapeutic intervention. In: Pharmaceutical Perspectives of Cancer Therapeutics. Springer Science and Business Media, LLC, NY, USA, 540 (2009).
  Google Scholar
• 128  Tan Z, Wu Y, Zhang H, Xiao X. CoCl₂-induced chemotherapy resistance in SW480 cells and its mechanism. Zhong Nan Da Xue Xue Bao Yi Xue Ban31(3),345–349 (2006).
  Medline CASGoogle Scholar
• 129  Semenza GL. Hypoxia-inducible factors: mediators of cancer progression and targets for cancer therapy. Trends Pharmacol. Sci.33(4),207–214 (2012).
  Medline CASGoogle Scholar
• 130  Xia Y, Choi H-K, Lee K. Recent advances in hypoxia-inducible factor (HIF)-1 inhibitors. Eur. J. Med. Chem.49,24–40 (2012).
  Medline CASGoogle Scholar
• 131  Kola L, Landis J. Can the pharmaceutical industry reduce attrition rates? Nat. Rev. Drug. Discov.3(8),1474–1776 (2004).
  Google Scholar
• 132  Adams DJ. The valley of death in anticancer drug development: a reassessment. Trends Pharmacol. Sci.33(4),173–180 (2012).
  Medline CASGoogle Scholar
• 133  Atkuri KR, Herzenberg LA, Herzenberg LA. Culturing at atmospheric oxygen levels impacts lymphocyte function. Proc. Natl Acad. Sci. USA102(10),3756–3759 (2005).
  Medline CASGoogle Scholar
• 134  Ivanovic Z. Hypoxia or in situ normoxia: the stem cell paradigm. J. Cell. Physiol.219(2),271–275 (2009).
  Medline CASGoogle Scholar
• 135  Gerweck LE, Seetharaman K. Cellular pH gradient in tumor versus normal tissue: potential exploitation for the treatment of cancer. Cancer Res.56(6),1194–1198 (1996).
  Medline CASGoogle Scholar
• 136  Gerweck LE, Kozin SV, Stocks SJ. The pH partition theory predicts the accumulation and toxicity of doxorubicin in normal and low-pH-adapted cells. Br. J. Cancer79(5–6),838–842 (1999).
  Medline CASGoogle Scholar
• 137  Wall ME, Wani MC. Camptothecin and taxol: discovery to clinic-thirteenth Bruce F. Cain memorial award lecture. Cancer Res.55(4),753–760 (1995).
  Medline CASGoogle Scholar
• 138  Hsiang YH, Hertzberg R, Hecht S, Liu LF. Camptothecin induces protein-linked DNA breaks via mammalian DNA topoisomerase I. J. Biol. Chem.260(27),14873–14878 (1985).
  Medline CASGoogle Scholar
• 139  Staker BL, Hjerrild K, Feese MD, Behnke CA, Burgin AB, Stewart L. The mechanism of topoisomerase I poisoning by a camptothecin analog. Proc. Natl Acad. Sci. USA99(24),15387–15392 (2002).
  Medline CASGoogle Scholar
• 140  Rapisarda A, Uranchimeg B, Sordet O, Pommier Y, Shoemaker RH, Melillo G. Topoisomerase I-mediated inhibition of hypoxia-inducible factor 1. Cancer Res.64(4),1475–1482 (2004).
  Medline CASGoogle Scholar
• 141  Baranello L, Bertozzi D, Fogli MV, Pommier Y, Capranico G. DNA topoisomerase I inhibition by camptothecin induces escape of RNA polymerase II from promoter-proximal pause site, antisense transcription and histone acetylation at the human HIF-1α gene locus. Nucleic Acids Res.38(1),159–171 (2010).
  Medline CASGoogle Scholar
• 142  Rothenberg ML. Irinotecan (CPT-11): recent developments and future directions – colorectal cancer and beyond. Oncologist6(1),66–80 (2001).
  Medline CASGoogle Scholar
• 143  Leblanc R, Catley LP, Hideshima T et al. Proteasome inhibitor PS-341 inhibits human myeloma cell growth in vivo and prolongs survival in a murine model. Cancer Res.62(17),4996–5000 (2002).
  Medline CASGoogle Scholar
• 144  Hideshima T, Richardson P, Chauhan D et al. The proteasome inhibitor PS-341 inhibits growth, induces apoptosis, and overcomes drug resistance in human multiple myeloma cells. Cancer Res.61(7),3071–3076 (2001).
  Medline CASGoogle Scholar
• 145  Hideshima T, Richardson PG, Anderson KC. Mechanism of action of proteasome inhibitors and deacetylase inhibitors and the biological basis of synergy in multiple myeloma. Mol. Cancer Ther.10(11),2034–2042 (2011).
  Medline CASGoogle Scholar
• 146  Shin DH, Chun Y-S, Lee DS, Huang LE, Park JW. Bortezomib inhibits tumor adaptation to hypoxia by stimulating the FIH-mediated repression of hypoxia-inducible factor-1. Blood111(6),3131–3136 (2008).
  Medline CASGoogle Scholar
• 147  Kaluz S, Kaluzova M, Stanbridge EJ. Proteasomal inhibition attenuates transcriptional activity of hypoxia-inducible factor 1 (HIF-1) via specific effect on the HIF-1α C-terminal activation domain. Mol. Cell. Biol.26(15),5895–5907 (2006).
  Medline CASGoogle Scholar
• 148  Befani C, Vlachostergios P, Hatzidaki E et al. Bortezomib represses HIF-1α protein expression and nuclear accumulation by inhibiting both PI3K/Akt/TOR and MAPK pathways in prostate cancer cells. J. Mol. Med.90(1),45–54 (2012).
  Medline CASGoogle Scholar
• 149  Bross PF, Kane R, Farrell AT et al. Approval summary for Bortezomib for injection in the treatment of multiple myeloma. Clin. Cancer Res.10(12),3954–3964 (2004).
  Medline CASGoogle Scholar
• 150  Ueda H, Nakajima H, Hori Y et al. FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties, and antitumor activity. J. Antibiot.47(3),301–310 (1994).
  Medline CASGoogle Scholar
• 151  Nakajima H, Kim YB, Terano H, Yoshida M, Horinouchi S. FR901228, a potent antitumor antibiotic, is a novel histone deacetylase inhibitor. Exp. Cell Res.241(1),126–133 (1998).
  Medline CASGoogle Scholar
• 152  Shigematsu N, Ueda H, Takase S, Tanaka H, Yamamoto K, Tada T. FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. II. Structure determination. J. Antibiot.47(3),311–314 (1994).
  Medline CASGoogle Scholar
• 153  Ueda H, Manda T, Matsumoto S et al. FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. III. Antitumor activities on experimental tumors in mice. J. Antibiot.47(3),315–323 (1994).
  Medline CASGoogle Scholar
• 154  Fath DM, Kong X, Liang D et al. Histone deacetylase inhibitors repress the transactivation potential of hypoxia-inducible factors independently of direct acetylation of HIF-1α. J. Biol. Chem.281(19),13612–13619 (2006).
  Medline CASGoogle Scholar
• 155  Qian DZ, Kachhap SK, Collis SJ et al. Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1α. Cancer Res.66(17),8814–8821 (2006).
  Medline CASGoogle Scholar
• 156  Rini BI. Temsirolimus, an inhibitor of mammalian target of rapamycin. Clin. Cancer Res.14(5),1286–1290 (2008).
  Medline CASGoogle Scholar
• 157  Thomas GV, Tran C, Mellinghoff IK et al. Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer. Nat. Med.12(1),122–127 (2006).
  Medline CASGoogle Scholar
• 158  Hudson CC, Liu M, Chiang GG et al. Regulation of hypoxia-inducible factor 1α expression and function by the mammalian target of rapamycin. Mol. Cell. Biol.22(20),7004–7014 (2002).
  Medline CASGoogle Scholar
• 159  Zhong H, Chiles K, Feldser D et al. Modulation of hypoxia-inducible factor 1α expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. Cancer Res.60(6),1541–1545 (2000).
  Medline CASGoogle Scholar
• 160  Kondapaka SB, Singh SS, Dasmahapatra GP, Sausville EA, Roy KK. Perifosine, a novel alkylphospholipid, inhibits protein kinase B activation. Mol. Cancer Ther.2(11),1093–1103 (2003).
  Medline CASGoogle Scholar
• 161  Ghobrial IM, Leleu X, Rubin N et al. Phase II trial of the novel oral Akt inhibitor perifosine in relapsed and/or refractory Waldenstrom macroglobulinemia (WM). J. Clin. Oncol.26(Suppl. 15),8546 (2008).
  Google Scholar
• 162  Lakhani NJ, Sarkar MA, Venitz J, Figg WD. 2-Methoxyestradiol, a promising anticancer agent. Pharmacotherapy23(2),165–172 (2003).
  Medline CASGoogle Scholar
• 163  Mabjeesh NJ, Escuin D, Lavallee TM et al. 2ME2 inhibits tumor growth and angiogenesis by disrupting microtubules and dysregulating HIF. Cancer Cell3(4),363–375 (2003).
  Medline CASGoogle Scholar
• 164  Carbonaro M, O’Brate A, Giannakakou P. Microtubule disruption targets HIF-1α mRNA to cytoplasmic P-bodies for translational repression. J. Cell Biol.192(1),83–99 (2011).
  Medline CASGoogle Scholar
• 165  Dahut WL, Lakhani NJ, Gulley JL et al. Phase I clinical trial of oral 2-methoxyestradiol, an antiangiogenic and apoptotic agent, in patients with solid tumors. Cancer Biol. Ther.5(1),22–27 (2006).
  Medline CASGoogle Scholar
• 166  Harrison MR, Hahn N, Pili R et al. Phase II study of 2-methoxyestradiol (2ME2) NanoCrystal Dispersion (NCD) in patients with taxane-refractory, metastatic hormone-refractory prostate cancer (HRPC). J. Clin. Oncol.26(Suppl. 15),5173 (2008).
  Google Scholar
• 167  Bruce J, Eickhoff J, Pili R et al. A Phase II study of 2-methoxyestradiol nanocrystal colloidal dispersion alone and in combination with sunitinib malate in patients with metastatic renal cell carcinoma progressing on sunitinib malate. Invest. New Drugs30(2),794–802 (2012).
  Medline CASGoogle Scholar
• 168  Formica JV, Waring MJ. Effect of phosphate and amino acids on echinomycin biosynthesis by Streptomyces echinatus. Antimicrob. Agents Chemother.24(5),735–741 (1983).
  Medline CASGoogle Scholar
• 169  Van Dyke M, Dervan P. Echinomycin binding sites on DNA. Science225(4667),1122–1127 (1984).
  Medline CASGoogle Scholar
• 170  Nickols NG, Jacobs CS, Farkas ME et al. Modulating hypoxia-inducible transcription by disrupting the HIF-1-DNA interface. ACS Chem. Biol.2(8),561–571 (2007).
  Medline CASGoogle Scholar
• 171  Kong D, Park EJ, Stephen AG et al. Echinomycin, a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity. Cancer Res.65(19),9047–9055 (2005).
  Medline CASGoogle Scholar
• 172  Onnis B, Rapisarda A, Melillo G. Development of HIF-1 inhibitors for cancer therapy. J. Cell. Mol. Med.13(9a),2780–2786 (2009).
  Medline CASGoogle Scholar
• 173  Deboer C, Meulman PA, Wnuk RJ, Peterson DH. Geldanamycin, a new antibiotic. J. Antibiot.23(9),442–447 (1970).
  Medline CASGoogle Scholar
• 174  Sato S, Fujita N, Tsuruo T. Modulation of Akt kinase activity by binding to Hsp90. Proc. Natl Acad. Sci. USA97(20),10832–10837 (2000).
  Medline CASGoogle Scholar
• 175  Whitesell L, Mimnaugh EG, De Costa B, Myers CE, Neckers LM. Inhibition of heat shock protein HSP90-pp60v-src heteroprotein complex formation by benzoquinone ansamycins: essential role for stress proteins in oncogenic transformation. Proc. Natl Acad. Sci. USA91(18),8324–8328 (1994).
  Medline CASGoogle Scholar
• 176  Dehner A, Furrer J, Richter K, Schuster I, Buchner J, Kessler H. NMR chemical shift perturbation study of the N-terminal domain of Hsp90 upon binding of ADP, AMP-PNP, geldanamycin, and radicicol. ChemBioChem4(9),870–877 (2003).
  Medline CASGoogle Scholar
• 177  Taipale M, Jarosz DF, Lindquist S. HSP90 at the hub of protein homeostasis: emerging mechanistic insights. Nat. Rev. Mol. Cell Biol.11(7),515–528 (2010).
  Medline CASGoogle Scholar
• 178  Bagatell R, Whitesell L. Altered Hsp90 function in cancer: a unique therapeutic opportunity. Mol. Cancer Ther.3(8),1021–1030 (2004).
  Medline CASGoogle Scholar
• 179  Minet E, Mottet D, Michel G et al. Hypoxia-induced activation of HIF-1: role of HIF-1alpha-Hsp90 interaction. FEBS Lett.460(2),251–256 (1999).
  Medline CASGoogle Scholar
• 180  Mabjeesh NJ, Post DE, Willard MT, Kaur B et al. Geldanamycin induces degradation of hypoxia-inducible factor 1alpha protein via the proteosome pathway in prostate cancer cells. Cancer Res.62(9),2478–2482 (2002).
  Medline CASGoogle Scholar
• 181  Supko JG, Hickman RL, Grever MR, Malspeis L. Preclinical pharmacologic evaluation of geldanamycin as an antitumor agent. Cancer Chemother. Pharmacol.36(4),305–315 (1995).
  Medline CASGoogle Scholar
• 182  Neckers LM. Chaperoning oncogenes: Hsp90 as a target of geldanamycin. Handb. Exp. Pharmacol.172,259–277 (2006).
  Medline CASGoogle Scholar
• 183  Richardson PG, Chanan-Khan AA, Alsina M et al. Tanespimycin monotherapy in relapsed multiple myeloma: results of a Phase I dose-escalation study. Br. J. Haematol.150(4),438–445 (2010).
  Medline CASGoogle Scholar
• 184  Solit DB, Osman I, Polsky D et al. Phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with metastatic melanoma. Clin. Cancer Res.14(24),8302–8307 (2008).
  Medline CASGoogle Scholar
• 185  Ronnen EA, Kondagunta GV, Ishill N et al. A Phase II trial of 17-(allylamino)-17-demethoxygeldanamycin in patients with papillary and clear cell renal cell carcinoma. Invest. New Drugs24(6),543–546 (2006).
  Medline CASGoogle Scholar
• 186  Heath EI, Hillman DW, Vaishampayan U et al. A Phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with hormone-refractory metastatic prostate cancer. Clin. Cancer Res.14(23),7940–7946 (2008).
  Medline CASGoogle Scholar
• 187  Pacey S, Wilson RH, Walton M et al. A Phase I study of the heat shock protein 90 inhibitor alvespimycin (17-DMAG) given intravenously to patients with advanced solid tumors. Clin. Cancer Res.17(6),1561–1570 (2011).
  Medline CASGoogle Scholar
• 188  Kaufmann SH, Karp JE, Litzow MR et al. Phase I and pharmacological study of cytarabine and tanespimycin in relapsed and refractory acute leukemia. Haematologica96(11),1619–1626 (2011).
  Medline CASGoogle Scholar
• 189  Hoelder S, Clarke PA, Workman P. Discovery of small molecule cancer drugs: successes, challenges and opportunities. Mol. Oncol.6(2),155–176 (2012).
  Medline CASGoogle Scholar
• 190  Valkov E, Sharpe T, Marsh M, Greive S, Hyvönen M. Targeting protein–protein interactions and fragment-based drug discovery. In: Fragment-Based Drug Discovery and X-Ray Crystallography. Davies TG, Hyvönen M (Eds). Springer Berlin/Heidelberg, Germany, 145–179 (2012).
  Google Scholar
• 191  Verdine GL, Hilinski GJ. All-hydrocarbon stapled peptides as synthetic cell-accessible mini-proteins. Drug Discov. Today Technol.9(1),e41–e47 (2012).
  CASGoogle Scholar
• 192  Shangary S, Wang S. Targeting the MDM2-p53 interaction for cancer therapy. Clin. Cancer Res.14(17),5318–5324 (2008).
  Medline CASGoogle Scholar
• 193  Higueruelo AP, Schreyer A, Bickerton GRJ, Pitt WR, Groom CR, Blundell TL. Atomic interactions and profile of small molecules disrupting protein–protein interfaces: the TIMBAL database. Chem. Biol. Drug Des.74(5),457–467 (2009).
  Medline CASGoogle Scholar
• 194  Fry DC. Drug-like inhibitors of protein-protein interactions: a structural examination of effective protein mimicry. Curr. Protein Pept. Sci.9(3),240–247 (2008).
  Medline CASGoogle Scholar
• 195  Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev.46(1–3),3–26 (2001).
  Medline CASGoogle Scholar
• 196  M. Monti S, T. Supuran C, De Simone G. Carbonic anhydrase IX as a target for designing novel anticancer drugs. Curr. Med. Chem.19(6),821–830 (2012).
  MedlineGoogle Scholar
• 197  Mylonis I, Lakka A, Tsakalof A, Simos G. The dietary flavonoid kaempferol effectively inhibits HIF-1 activity and hepatoma cancer cell viability under hypoxic conditions. Biochem. Biophys. Res. Commun.398(1),74–78 (2010).
  Medline CASGoogle Scholar
• 198  Nagle D-G, Zhou Y-D. Natural product-based inhibitors of hypoxia-inducible factor-1 (HIF-1). Curr. Drug Targets7(3),355–369 (2006).
  Medline CASGoogle Scholar
• 199  Lakka A, Mylonis I, Bonanou S, Simos G, Tsakalof A. Isolation of hypoxia-inducible factor 1 (HIF-1) inhibitors from frankincense using a molecularly imprinted polymer. Invest. New Drugs29(5),1081–1089 (2011).
  Medline CASGoogle Scholar
• 200  Lee K, Zhang H, Qian DZ, Rey S, Liu JO, Semenza GL. Acriflavine inhibits HIF-1 dimerization, tumor growth, and vascularization. Proc. Natl Acad. Sci. USA106(42),17910–17915 (2009).
  Medline CASGoogle Scholar
• 201  Scheuermann TH, Tomchick DR, Machius M, Guo Y, Bruick RK, Gardner KH. Artificial ligand binding within the HIF2a PAS-B domain of the HIF2 transcription factor. Proc. Natl Acad. Sci. USA106(2),450–455 (2009).
  Medline CASGoogle Scholar
• 202  Kung AL, Zabludoff SD, France DS et al. Small molecule blockade of transcriptional coactivation of the hypoxia-inducible factor pathway. Cancer Cell6(1),33–43 (2004).
  Medline CASGoogle Scholar
• 203  Cook KM, Hilton ST, Mecinović J, Motherwell WB, Figg WD, Schofield CJ. Epidithiodiketopiperazines block the interaction between hypoxia-inducible factor-1α (HIF-1α) and p300 by a zinc ejection mechanism. J. Biol. Chem.284(39),26831–26838 (2009).
  Medline CASGoogle Scholar
• 204  Henchey LK, Kushal S, Dubey R, Chapman RN, Olenyuk BZ, Arora PS. Inhibition of hypoxia inducible factor 1-transcription coactivator interaction by a hydrogen bond surrogate α-helix. J. Am. Chem. Soc.132(3),941–943 (2009).
  Google Scholar
• 205  Post DE, Van Meir EG. A novel hypoxia-inducible factor (HIF) activated oncolytic adenovirus for cancer therapy. Oncogene22(14),2065–2072 (2003).
  Medline CASGoogle Scholar
• 206  Post DE, Devi NS, Li ZC et al. Cancer therapy with a replicating oncolytic adenovirus targeting the hypoxic microenvironment of tumors. Clin. Cancer Res.10(24),8603–8612 (2004).
  Medline CASGoogle Scholar
• 207  Post DE, Sandberg EM, Kyle MM et al. Targeted cancer gene therapy using a hypoxia inducible factor-dependent oncolytic adenovirus armed with interleukin-4. Cancer Res.67(14),6872–6881 (2007).
  Medline CASGoogle Scholar
• 208  Tan C, de Noronha RG, Roecker AJ et al. Identification of a novel small-molecule inhibitor of the hypoxia-inducible factor 1 pathway. Cancer Res.65(2),605–612 (2005).
  Medline CASGoogle Scholar
• 209  Narita T, Yin S, Gelin CF et al. Identification of a Novel Small Molecule HIF-1 alpha Translation Inhibitor. Clin. Cancer Res.15(19),6128–6136 (2009).
  Medline CASGoogle Scholar
• 210  Tan C, de Noronha RG, Devi NS et al. Sulfonamides as a new scaffold for hypoxia inducible factor pathway inhibitors. Bioorg. Med. Chem. Lett.21(18),5528–5532 (2011).
  Medline CASGoogle Scholar
• 211  Mooring SR, Jin H, Devi NS et al. Design and synthesis of novel small-molecule inhibitors of the hypoxia inducible factor pathway. J. Med. Chem.54(24),8471–8489 (2011).
  Medline CASGoogle Scholar
• 212  Mun J, Jabbar AA, Devi NS, Liu Y, Van Meir EG, Goodman MM. Structure–activity relationship of 2,2-dimethyl-2H-chromene based arylsulfonamide analogs of 3,4-dimethoxy-N-[(2,2-dimethyl-2H-chromen-6-yl)methyl]-N-phenylbenzenesulfonamide, a novel small molecule hypoxia inducible factor-1 (HIF-1) pathway inhibitor and anti-cancer agent. Bioorg. Med. Chem.20(14),4590–4597 (2012).
  Medline CASGoogle Scholar
• 213  Mun J, Jabbar AA, Devi NS et al. Design and in vitro activities of N-alkyl-N-[(8-R-2,2-dimethyl-2H-chromen-6-yl)methyl]heteroarylsulfonamides, novel, small-molecule hypoxia inducible factor-1 pathway inhibitors and anticancer agents. J. Med. Chem.55(15),6738–6750 (2012).
  Medline CASGoogle Scholar
• 214  Shi Q, Yin S, Kaluz S et al. Binding model for the interaction of anticancer arylsulfonamides with the p300 transcription cofactor. ACS Med. Chem. Lett.3(8),620–625 (2012).
  Medline CASGoogle Scholar
• 215  Yin S, Kaluz S, Devi NS et al. Arylsulfonamide KCN1 inhibits in vivo glioma growth and interferes with HIF signaling by disrupting HIF-1 alpha interaction with cofactors p300/CBP. Clin. Cancer Res.18(24),6623–6633 (2012).
  Medline CASGoogle Scholar
• 216  Wang W, Ao L, Rayburn ER et al. KCN1, a novel synthetic sulfonamide anticancer agent: in vitro and in vivo anti-pancreatic cancer activities and preclinical pharmacology. PLoS ONE7(9),e44883 (2012).
  Medline CASGoogle Scholar
• 301  American Cancer Society. Cancer facts and figures 2011. www.cancer.org/Research/CancerFactsFigures/CancerFactsFigures/cancer-facts-figures-2011 (Accessed 11 April 2012)
  Google Scholar
• 302  World Cancer Research Fund International. General world cancer statistics: GLOBOCAN 2008 database. www.wcrf.org/cancer_statistics/world_cancer_statistics.php (Accessed 1 April 2012)
  Google Scholar
• 303  US FDA approves topotecan hydrochloride (hycamtin) in combination with cisplatin for the treatment of Stage IVB recurrent or persistent carcinoma of the cervix. www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm095638.htm (Accessed 30 April 2012)
  Google Scholar
• 304  GlaxoSmith Kline receives approval for hycamtin (topotecan) capsules for the treatment of relapsed small cell lung cancer. www.drugs.com/newdrugs/gsk-receives-approval-hycamtin-topotecan-capsules-relapsed-small-cell-lung-cancer-671.html (Accessed 4 May 2012)
  Google Scholar
• 305  National Cancer Institute. Romidepsin. www.cancer.gov/cancertopics/druginfo/romidepsin (Accessed 1 June 2011)
  Google Scholar
• 306  US FDA approves new drug for advanced kidney cancer. www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/2007/ucm108924.htm (Accessed 4 May 2012)
  Google Scholar
• 307  Genetic Engineering & Biotechnology News. Aeterna Zentaris regains North American rights to Akt inhibitor from Keryx. www.genengnews.com/gen-news-highlights/aeterna-zentaris-regains-north-american-rights-to-akt-inhibitor-from-keryx/81246731/ (Accessed 11 May 2012)
  Google Scholar
• 308  Patent Database Search Results: ISD 1/1/2000->12/31/2012 AND HIF AND cancer AND inhibitor in US Patent Collection. http://patft.uspto.gov/netacgi/nph-Parser?Sect1=PTO2&Sect2=HITOFF&u=%2Fnetahtml%2FPTO%2Fsearch-adv.htm&r=0&f=S&l=50&d=PTXT&RS=%28%28%28ISD%2F20120101-%3E20121231+AND+HIF%29+AND+Cancer%29+AND+inhibitor%29&Refine=Refine+Search&Refine=Refine+Search&Query=ISD%2F1%2F1%2F2000-%3E12%2F31%2F2012+AND+HIF+AND+Cancer+AND+inhibitor (Accessed 26 February 2013)
  Google Scholar
• 309  Web of Knowledge – All Database Results: Topic=(HIF AND CANCER AND INHIBITOR) Timespan=2000-2012. http://apps.webofknowledge.com/summary.do?SID=1F83DLk7akON2aaKN9E&product=UA&qid=18&search_mode=GeneralSearch (Accessed 26 February 2013)
  Google Scholar
• 310  Search of: HIF and cancer – List Results – ClinicalTrials.gov. www.clinicaltrials.gov/ct2/results?term=hif+and+cancer+&Search=Search (Accessed 26 February 2013)
  Google Scholar