The impact of O2 availability on human cancer

Nature Reviews Cancer

Volumn 8, Issue 12, 2008, Pages 967-975

  Bertout, Jessica A ^a,b   Patel, Shetal A ^a,c   Simon, M Celeste ^a,c,d  

^a Abramson Family Cancer Research Institute

^b School of Veterinary Medicine

^c School of Medicine

^d UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 FLUORO 3 (2 NITRO 1 IMIDAZOLYL) 2 PROPANOL; BEVACIZUMAB; COPPER DIACETYL BIS(N4 METHYLTHIOSEMICARBAZONE); CYCLIN D; DNA TOPOISOMERASE INHIBITOR; ETANIDAZOLE; ETANIDAZOLE PENTAFLUORIDE; EVEROLIMUS; FLUORODEOXYGLUCOSE F 18; GEFITINIB; HEAT SHOCK PROTEIN 90 INHIBITOR; HISTONE DEACETYLASE INHIBITOR; HYPOXIA INDUCIBLE FACTOR; MAMMALIAN TARGET OF RAPAMYCIN; MISONIDAZOLE; NITROIMIDAZOLE DERIVATIVE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN BID; PROTEIN KINASE B; PROTEIN LYSINE 6 OXIDASE; PROTEIN P300; RAS PROTEIN; RECEPTOR FOR ACTIVATED C KINASE 1; SORAFENIB; TIRAPAZAMINE; TRANSCRIPTION FACTOR; TRANSFORMING GROWTH FACTOR ALPHA; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULOTROPIN A; VASCULOTROPIN ANTIBODY; BASIC HELIX LOOP HELIX TRANSCRIPTION FACTOR;

ANGIOGENESIS; CANCER TISSUE; CELL METABOLISM; COLORECTAL CANCER; DOUBLE STRANDED DNA BREAK; DRUG EFFICACY; DRUG TARGETING; GENE ACTIVATION; GROWTH REGULATION; HUMAN; HYPOXIA; LIVER CELL CARCINOMA; LUNG CANCER; METASTASIS; NEOPLASM; NONHUMAN; OXYGEN CONCENTRATION; OXYGEN SENSING; OXYGEN TENSION; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; RADIOSENSITIVITY; REGULATORY MECHANISM; REVIEW; TISSUE OXYGENATION; TUMOR GROWTH; AEROBIC METABOLISM; ANIMAL; ANIMAL MODEL; CELL DIVISION; CELL HYPOXIA; GLYCOLYSIS; METABOLISM; NECROSIS; OXYGEN CONSUMPTION; PATHOLOGY; PHYSIOLOGY;

AEROBIOSIS; ANIMALS; BASIC HELIX-LOOP-HELIX TRANSCRIPTION FACTORS; CELL DIVISION; CELL HYPOXIA; GLYCOLYSIS; HUMANS; MODELS, ANIMAL; NECROSIS; NEOPLASMS; OXYGEN CONSUMPTION;

EID: 57149142495     PISSN: 1474175X     EISSN: 14741768     Source Type: Journal    
DOI: 10.1038/nrc2540     Document Type: Review

References (156)

1. Warburg, O. On the origin of cancer cells. Science 123, 309-314 (1956).
2. Denko, N. C. Hypoxia, HIF1 and glucose metabolism in the solid tumour. Nature Rev. Cancer 8, 705-713 (2008).
3. Gatenby, R. A. & Gillies, R. J. Why do cancers have high aerobic glycolysis? Nature Rev. Cancer 4, 891-899 (2004).
4. Deberardinis, R. J., Sayed, N., Ditsworth, D. & Thompson, C. B. Brick by brick: metabolism and tumor cell growth. Curr. Opin. Genet. Dev. 18, 54-61 (2008).
5. Gray, L. H., Conger, A. D., Ebert, M., Hornsey, S. & Scott, O. C. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br. J. Radiol. 26, 638-648 (1953).
6. Thomlinson, R. H. & Gray, L. H. The histological structure of some human lung cancers and the possible implications for radiotherapy. Br. J. Cancer 9, 539-549 (1955).
7. Thomlinson, R. H. Tumour anoxia and the response to radiation. Sci. Basis Med. Annu. Rev., 74-90 (1965).
8. Simon, M. C., Liu, L., Barnhart, B. C. & Young, R. M. Hypoxia-induced signaling in the cardiovascular system. Annu. Rev. Physiol. 70, 51-71 (2008).
9. Powers, W. E. & Tolmach, L. J. Demonstration of an anoxic component in a mouse tumor-cell population by in vivo assay of survival following irradiation. Radiology 83, 328-336 (1964).
10. Churchill-Davidson, I. Oxygenation in radiotherapy of malignant disease of the upper air passages. the oxygen effect of radiotherapy. Proc. R. Soc. Med. 57, 635-638 (1964).
11. Okunieff, P., Fenton, B. & Chen, Y. Past, present, and future of oxygen in cancer research. Adv. Exp. Med. Biol. 566, 213-222 (2005).
12. Vaupel, P., Schlenger, K. & Hoeckel, M. Blood flow and tissue oxygenation of human tumors: an update. Adv. Exp. Med. Biol. 317, 139-151 (1992).
13. Urtasun, R. C., Chapman, J. D., Raleigh, J. A., Franko, A. J. & Koch, C. J. Binding of [3H]misonidazole to solid human tumors as a measure of tumor hypoxia. Int. J. Radiat. Oncol. Biol. Phys. 12, 1263-1267 (1986).
14. 2 at the cellular level. Br. J. Cancer 54, 453-457 (1986).
15. Chapman, J. D. Measurement of tumor hypoxia by invasive and non-invasive procedures: a review of recent clinical studies. Radiother. Oncol. 20 (Suppl. 1), 13-19 (1991).
16. 2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation. Nature Med. 3, 177-182 (1997).
17. Chaplin, D. J., Durand, R. E. & Olive, P. L. Acute hypoxia in tumors: implications for modifiers of radiation effects. Int. J. Radiat. Oncol. Biol. Phys. 12, 1279-1282 (1986).
18. Dewhirst, M. W., Cao, Y. & Moeller, B. Cycling hypoxia and free radicals regulate angiogenesis and radiotherapy response. Nature Rev. Cancer 8, 425-437 (2008).
19. Barach, A. L. & Bickerman, H. A. The effect of anoxia on tumor growth with special reference to sarcoma 180 implanted in C57 mice. Cancer Res. 14, 672-676 (1954).
20. Thomlinson, R. H. Hypoxia and tumours. J. Clin. Pathol. Suppl (R. Coll. Pathol.) 11, 105-113 (1977).
21. Churchill-Davidson, I., Sanger, C. & Thomlinson, R. H. High-pressure oxygen and radiotherapy. Lancet 268, 1091-1095 (1955).
22. Hall, E. J. & Giaccia, A. Radiobiology for the Radiologist (Lippincott Williams & Wilkins, Philadelphia, 2006).
23. Deschner, E. E. & Gray, L. H. Influence of oxygen tension on x-ray-induced chromosomal damage in Ehrlich ascites tumor cells irradiated in vitro and in vivo. Radiat. Res. 11, 115-146 (1959).
24. Churchill-Davidson, I., Sanger, C. & Thomlinson, R. H. Oxygenation in radiotherapy. II. Clinical application. Br. J. Radiol 30, 406-422 (1957).
25. Dewey, D. L. Effect of oxygen and nitric oxide on the radio-sensitivity of human cells in tissue culture. Nature 186, 780-782 (1960).
26. Hewitt, H. B. & Wilson, C. W. The effect of tissue oxygen tension on the radiosensitivity of leukaemia cells irradiated in situ in the livers of leukaemic mice. Br. J. Cancer 13, 675-684 (1959).
27. Gray, L. H. Radiobiologic basis of oxygen as a modifying factor in radiation therapy. Am. J. Roentgenol Radium Ther. Nucl. Med. 85, 803-815 (1961).
28. Teicher, B. A. Hypoxia and drug resistance. Cancer Metastasis Rev. 13, 139-168 (1994).
29. Teicher, B. A., Lazo, J. S. & Sartorelli, A. C. Classification of antineoplastic agents by their selective toxicities toward oxygenated and hypoxic tumor cells. Cancer Res. 41, 73-81 (1981).
30. Henk, J. M. Does hyperbaric oxygen have a future in radiation therapy? Int. J. Radiat. Oncol. Biol. Phys. 7, 1125-1128 (1981).
31. Brown, J. M. Clinical trials of radiosensitizers: what should we expect? Int. J. Radiat. Oncol. Biol. Phys. 10, 425-429 (1984).
32. Kallman, R. F. & Dorie, M. J. Tumor oxygenation and reoxygenation during radiation therapy: their importance in predicting tumor response. Int. J. Radiat. Oncol. Biol. Phys. 12, 681-685 (1986).
33. Coleman, C. N. Modulating the radiation response. Stem Cells 14, 10-15 (1996).
34. Steel, G. G., McMillan, T. J. & Peacock, J. H. The radiobiology of human cells and tissues. In vitro radiosensitivity. The picture has changed in the 1980s. Int. J. Radiat. Biol. 56, 525-537 (1989).
35. Brown, J. M. & Giaccia, A. J. Tumour hypoxia: the picture has changed in the 1990s. Int. J. Radiat. Biol. 65, 95-102 (1994).
36. Blumenson, L. E. & Bross, I. D. A possible mechanism for enhancement of increased production of tumor angiogenic factor. Growth 40, 205-209 (1976).
37. van den Brenk, H. A., Moore, V., Sharpington, C. & Orton, C. Production of metastases by a primary tumour irradiated under aerobic and anaerobic conditions in vivo. Br. J. Cancer 26, 402-412 (1972).
38. Young, S. D., Marshall, R. S. & Hill, R. P. Hypoxia induces DNA overreplication and enhances metastatic potential of murine tumor cells. Proc. Natl Acad. Sci. USA 85, 9533-9537 (1988).
39. Young, S. D. & Hill, R. P. Effects of reoxygenation on cells from hypoxic regions of solid tumors: analysis of transplanted murine tumors for evidence of DNA overreplication. Cancer Res. 50, 5031-5038 (1990).
40. Heacock, C. S. & Sutherland, R. M. Enhanced synthesis of stress proteins caused by hypoxia and relation to altered cell growth and metabolism. Br. J. Cancer 62, 217-225 (1990).
41. Sciandra, J. J., Subjeck, J. R. & Hughes, C. S. Induction of glucose-regulated proteins during anaerobic exposure and of heat-shock proteins after reoxygenation. Proc. Natl Acad. Sci. USA 81, 4843-4847 (1984).
42. Murphy, B. J., Laderoute, K. R., Short, S. M. & Sutherland, R. M. The identification of heme oxygenase as a major hypoxic stress protein in Chinese hamster ovary cells. Br. J. Cancer 64, 69-73 (1991).
43. Roll, D. E., Murphy, B. J., Laderoute, K. R., Sutherland, R. M. & Smith, H. C. Oxygen regulated 80 kDa protein and glucose regulated 78 kDa protein are identical. Mol. Cell Biochem. 103, 141-148 (1991).
44. Shweiki, D., Itin, A., Soffer, D. & Keshet, E. Vascular endothelial growth factor induced by hypoxia may mediate hypoxia-initiated angiogenesis. Nature 359, 843-845 (1992).
45. Shreeniwas, R. et al. Hypoxia-mediated induction of endothelial cell interleukin-1α. An autocrine mechanism promoting expression of leukocyte adhesion molecules on the vessel surface. J. Clin. Invest. 90, 2333-2339 (1992).
46. Kourembanas, S., Marsden, P. A., McQuillan, L. P. & Faller, D. V. Hypoxia induces endothelin gene expression and secretion in cultured human endothelium. J. Clin. Invest. 88, 1054-1057 (1991).
47. Kourembanas, S., Hannan, R. L. & Faller, D. V. Oxygen tension regulates the expression of the platelet-derived growth factor-B chain gene in human endothelial cells. J. Clin. Invest. 86, 670-674 (1990).
48. Goldberg, M. A., Dunning, S. P. & Bunn, H. F. Regulation of the erythropoietin gene: evidence that the oxygen sensor is a heme protein. Science 242, 1412-1415 (1988).
49. Robin, E. D., Murphy, B. J. & Theodore, J. Coordinate regulation of glycolysis by hypoxia in mammalian cells. J. Cell Physiol. 118, 287-290 (1984).
50. Anderson, G. R., Stoler, D. L. & Scarcello, L. A. Normal fibroblasts responding to anoxia exhibit features of the malignant phenotype. J. Biol. Chem. 264, 14885-14892 (1989).
51. Price, B. D. & Calderwood, S. K. Gadd45 and Gadd153 messenger RNA levels are increased during hypoxia and after exposure of cells to agents which elevate the levels of the glucose-regulated proteins. Cancer Res. 52, 3814-3817 (1992).
52. 2 tension. Proc. Natl Acad. Sci. USA 92, 5510-5514 (1995).
53. Beck, I., Ramirez, S., Weinmann, R. & Caro, J. Enhancer element at the 3′-flanking region controls transcriptional response to hypoxia in the human erythropoietin gene. J. Biol. Chem. 266, 15563-15566 (1991).
54. Pugh, C. W., Tan, C. C., Jones, R. W. & Ratcliffe, P. J. Functional analysis of an oxygen-regulated transcriptional enhancer lying 3′ to the mouse erythropoietin gene. Proc. Natl Acad. Sci. USA 88, 10553-10557 (1991).
55. Semenza, G. L., Nejfelt, M. K., Chi, S. M. & Antonarakis, S. E. Hypoxia-inducible nuclear factors bind to an enhancer element located 3′ to the human erythropoietin gene. Proc. Natl Acad. Sci. USA 88, 5680-5684 (1991).
56. Madan, A. & Curtin, P. T. A 24-base-pair sequence 3′ to the human erythropoietin gene contains a hypoxia-responsive transcriptional enhancer. Proc. Natl Acad. Sci. USA 90, 3928-3932 (1993).
57. Semenza, G. L. & Wang, G. L. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol. Cell. Biol. 12, 5447-5454 (1992).
58. Wang, G. L. & Semenza, G. L. Characterization of hypoxia-inducible factor 1 and regulation of DNA binding activity by hypoxia. J. Biol. Chem. 268, 21513-21518 (1993).
59. 2 tension. Am. J. Physiol. 271, C1172-C1180 (1996).
60. Wouters, B. & Koritzinsky, M. Hypoxia signalling through mTOR and the unfolded protein response in cancer. Nature Rev. Cancer 8, 851-864 (2008).
61. Simon, M. C. & Keith, B. The role of oxygen availability in embryonic development and stem cell function. Nature Rev. Mol. Cell Biol. 9, 285-296 (2008).
62. Jain, S., Maltepe, E., Lu, M. M., Simon, C. & Bradfield, C. A. Expression of ARNT, ARNT2, HIF1α, HIF2α and Ah receptor mRNAs in the developing mouse. Mech. Dev. 73, 117-123 (1998).
63. Tian, H., McKnight, S. L. & Russell, D. W. Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. Genes Dev. 11, 72-82 (1997).
64. Wiesener, M. S. et al. Widespread hypoxia-inducible expression of HIF-2α in distinct cell populations of different organs. FASEB J. 17, 271-273 (2003).
65. Gu, Y. Z., Moran, S. M., Hogenesch, J. B., Wartman, L. & Bradfield, C. A. Molecular characterization and chromosomal localization of a third alpha-class hypoxia inducible factor subunit, HIF3α. Gene Expr. 7, 205-213 (1998).
66. Makino, Y. et al. Inhibitory PAS domain protein is a negative regulator of hypoxia-inducible gene expression. Nature 414, 550-554 (2001).
67. 2-dependent degradation domain via the ubiquitin-proteasome pathway. Proc. Natl Acad. Sci. USA 95, 7987-7992 (1998).
68. Salceda, S. & Caro, J. Hypoxia-inducible factor 1α (HIF-1α) protein is rapidly degraded by the ubiquitin-proteasome system under normoxic conditions. Its stabilization by hypoxia depends on redox-induced changes. J. Biol. Chem. 272, 22642-22647 (1997).
69. Kallio, P. J., Wilson, W. J., O'Brien, S., Makino, Y. & Poellinger, L. Regulation of the hypoxia-inducible transcription factor 1alpha by the ubiquitin-proteasome pathway. J. Biol. Chem. 274, 6519-6525 (1999).
70. Maxwell, P. H. et al. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399, 271-275 (1999).
71. Cockman, M. E. et al. Hypoxia inducible factor-α binding and ubiquitylation by the von Hippel-Lindau tumor suppressor protein. J. Biol. Chem. 275, 25733-25741 (2000).
72. Kamura, T. et al. Activation of HIF1α ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex. Proc. Natl Acad. Sci. USA 97, 10430-10435 (2000).
73. Ohh, M. et al. Ubiquitination of hypoxia-inducible factor requires direct binding to the β-domain of the von Hippel-Lindau protein. Nature Cell Biol. 2, 423-427 (2000).
74. Tanimura, T. & Shepard, T. H. Glucose metabolism by rat embryos in vitro. Proc. Soc. Exp. Biol. Med. 135, 51-54 (1970).
75. Stebbins, C. E., Kaelin, W. G. Jr & Pavletich, N. P. Structure of the VHL-ElonginC-ElonginB complex: implications for VHL tumor suppressor function. Science 284, 455-461 (1999).
76. 2-regulated prolyl hydroxylation. Science 292, 468-472 (2001).
77. 2 sensing. Science 292, 464-468 (2001).
78. Yu, F., White, S. B., Zhao, Q. & Lee, F. S. HIF-1α binding to VHL is regulated by stimulus-sensitive proline hydroxylation. Proc. Natl Acad. Sci. USA 98, 9630-9635 (2001).
79. Epstein, A. C. et al. C. elegans EGL-9 and mammalian homologs define a family of dioxygenases that regulate HIF by prolyl hydroxylation. Cell 107, 43-54 (2001).
80. Bruick, R. K. & McKnight, S. L. A conserved family of prolyl-4-hydroxylases that modify HIF. Science 294, 1337-1340 (2001).
81. Ivan, M. et al. Biochemical purification and pharmacological inhibition of a mammalian prolyl hydroxylase acting on hypoxia-inducible factor. Proc. Natl Acad. Sci. USA 99, 13459-13464 (2002).
82. Mahon, P. C., Hirota, K. & Semenza, G. L. FIH-1: a novel protein that interacts with HIF-1α and VHL to mediate repression of HIF-1 transcriptional activity. Genes Dev. 15, 2675-2686 (2001).
83. Hewitson, K. S. et al. Hypoxia-inducible factor (HIF) asparagine hydroxylase is identical to factor inhibiting HIF (FIH) and is related to the cupin structural family. J. Biol. Chem. 277, 26351-26355 (2002).
84. Lando, D. et al. FIH-1 is an asparaginyl hydroxylase enzyme that regulates the transcriptional activity of hypoxia-inducible factor. Genes Dev. 16, 1466-1471 (2002).
85. Lando, D., Peet, D. J., Whelan, D. A., Gorman, J. J. & Whitelaw, M. L. Asparagine hydroxylation of the HIF transactivation domain a hypoxic switch. Science 295, 858-861 (2002).
86. Maxwell, P. H., Pugh, C. W. & Ratcliffe, P. J. Activation of the HIF pathway in cancer. Curr. Opin. Genet. Dev. 11, 293-299 (2001).
87. Semenza, G. L. Targeting HIF-1 for cancer therapy. Nature Rev. Cancer 3, 721-732 (2003).
88. Giaccia, A., Siim, B. G. & Johnson, R. S. HIF-1 as a target for drug development. Nature Rev. Drug Discov. 2, 803-811 (2003).
89. Birner, P. et al. Overexpression of hypoxia-inducible factor 1α is a marker for an unfavorable prognosis in early-stage invasive cervical cancer. Cancer Res. 60, 4693-4696 (2000).
90. Schindl, M. et al. Overexpression of hypoxia-inducible factor 1α is associated with an unfavorable prognosis in lymph node-positive breast cancer. Clin. Cancer Res. 8, 1831-1837 (2002).
91. Bos, R. et al. Levels of hypoxia-inducible factor-1 α during breast carcinogenesis. J. Natl Cancer Inst. 93, 309-314 (2001).
92. Birner, P. et al. Expression of hypoxia-inducible factor-1 α in oligodendrogliomas: its impact on prognosis and on neoangiogenesis. Cancer 92, 165-171 (2001).
93. Birner, P., Schindl, M., Obermair, A., Breitenecker, G. & Oberhuber, G. Expression of hypoxia-inducible factor 1α in epithelial ovarian tumors: its impact on prognosis and on response to chemotherapy. Clin. Cancer Res. 7, 1661-1668 (2001).
94. Sivridis, E., Giatromanolaki, A., Gatter, K. C., Harris, A. L. & Koukourakis, M. I. Association of hypoxia-inducible factors 1α and 2α with activated angiogenic pathways and prognosis in patients with endometrial carcinoma. Cancer 95, 1055-1063 (2002).
95. Aebersold, D. M. et al. Expression of hypoxia-inducible factor-1α: a novel predictive and prognostic parameter in the radiotherapy of oropharyngeal cancer. Cancer Res. 61, 2911-2916 (2001).
96. Giatromanolaki, A. et al. Relation of hypoxia inducible factor 1 α and 2 α in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival. Br. J. Cancer 85, 881-890 (2001).
97. Holmquist-Mengelbier, L. et al. Recruitment of HIF-1α and HIF-2α to common target genes is differentially regulated in neuroblastoma: HIF-2α promotes an aggressive phenotype. Cancer Cell 10, 413-423 (2006).
98. Khatua, S. et al. Overexpression of the EGFR/FKBP12/HIF-2α pathway identified in childhood astrocytomas by angiogenesis gene profiling. Cancer Res. 63, 1865-1870 (2003).
99. Koukourakis, M. I. et al. Hypoxia-inducible factor (HIF1A and HIF2A), angiogenesis, and chemoradiotherapy outcome of squamous cell head-and-neck cancer. Int. J. Radiat. Oncol. Biol. Phys. 53, 1192-1202 (2002).
100. Beasley, N. J. et al. Hypoxia-inducible factors HIF-1α and HIF-2α in head and neck cancer: relationship to tumor biology and treatment outcome in surgically resected patients. Cancer Res. 62, 2493-2497 (2002).
101. Volm, M. & Koomagi, R. Hypoxia-inducible factor (HIF-1) and its relationship to apoptosis and proliferation in lung cancer. Anticancer Res. 20, 1527-1533 (2000).
102. Mandriota, S. J. et al. HIF activation identifies early lesions in VHL kidneys: evidence for site-specific tumor suppressor function in the nephron. Cancer Cell 1, 459-468 (2002).
103. Raval, R. R. et al. Contrasting properties of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in von Hippel-Lindau-associated renal cell carcinoma. Mol. Cell. Biol. 25, 5675-5686 (2005).
104. Maxwell, P. H. et al. Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc. Natl Acad. Sci. USA 94, 8104-8109 (1997).
105. Ryan, H. E. et al. Hypoxia-inducible factor-1α is a positive factor in solid tumor growth. Cancer Res. 60, 4010-4015 (2000).
106. Kung, A. L., Wang, S., Klco, J. M., Kaelin, W. G. & Livingston, D. M. Suppression of tumor growth through disruption of hypoxia-inducible transcription. Nature Med. 6, 1335-1340 (2000).
107. Liao, D., Corle, C., Seagroves, T. N. & Johnson, R. S. Hypoxia-inducible factor-1α is a key regulator of metastasis in a transgenic model of cancer initiation and progression. Cancer Res. 67, 563-572 (2007).
108. Hiraga, T., Kizaka-Kondoh, S., Hirota, K., Hiraoka, M. & Yoneda, T. Hypoxia and hypoxia-inducible factor-1 expression enhance osteolytic bone metastases of breast cancer. Cancer Res. 67, 4157-4163 (2007).
109. Koukourakis, M. I. et al. Endogenous markers of two separate hypoxia response pathways (hypoxia inducible factor 2α and carbonic anhydrase 9) are associated with radiotherapy failure in head and neck cancer patients recruited in the CHART randomized trial. J. Clin. Oncol. 24, 727-735 (2006).
110. Graeber, T. G. et al. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours [see comments]. Nature 379, 88-91 (1996).
111. An, W. G. et al. Stabilization of wild-type p53 by hypoxia-inducible factor 1α. Nature 392, 405-408 (1998).
112. Koshiji, M. et al. HIF-1α induces cell cycle arrest by functionally counteracting Myc. EMBO J. 23, 1949-1956 (2004).
113. Gordan, J. D., Bertout, J. A., Hu, C. J., Diehl, J. A. & Simon, M. C. HIF-2α promotes hypoxic cell proliferation by enhancing c-myc transcriptional activity. Cancer Cell 11, 335-347 (2007).
114. Gordan, J. D., Thompson, C. B. & Simon, M. C. HIF and c-Myc: sibling rivals for control of cancer cell metabolism and proliferation. Cancer Cell 12, 108-113 (2007).
115. Schwarz, G. Ueber Desensibilisierung gegen rontgen- und radiumstrahlen. Munchener Medizinische Wochenschrift 24, 1-2 (1909) (in German).
116. Brown, J. M. Tumor hypoxia in cancer therapy. Meth. Enzymol. 435 (2007).
117. Overgaard, J. Hypoxic radiosensitization: adored and ignored. J. Clin. Oncol. 25, 4066-4074 (2007).
118. Urtasun, R. C., Band, P. R., Chapman, J. D. & Feldstein, M. L. Radiation plus metronidazole for glioblastoma. N. Engl. J. Med. 296, 757 (1977).
119. Zeman, E. M., Brown, J. M., Lemmon, M. J., Hirst, V. K. & Lee, W. W. SR-4233: a new bioreductive agent with high selective toxicity for hypoxic mammalian cells. Int. J. Radiat. Oncol. Biol. Phys. 12, 1239-1242 (1986).
120. Brown, J. M. & Wilson, W. R. Exploiting tumour hypoxia in cancer treatment. Nature Rev. Cancer 4, 437-447 (2004).
121. Rischin, D. et al. Tirapazamine, cisplatin, and radiation versus fluorouracil, cisplatin, and radiation in patients with locally advanced head and neck cancer: a randomized phase II trial of the Trans-Tasman Radiation Oncology Group (TROG 98.02). J. Clin. Oncol. 23, 79-87 (2005).
122. von Pawel, J. et al. Tirapazamine plus cisplatin versus cisplatin in advanced non-small-cell lung cancer: A report of the international CATAPULT I study group. Cisplatin and Tirapazamine in Subjects with Advanced Previously Untreated Non-Small-Cell Lung Tumors. J. Clin. Oncol. 18, 1351-1359 (2000).
123. Shrieve, D. C. & Harris, J. W. The in vitro sensitivity of chronically hypoxic EMT6/SF cells to X-radiation and hypoxic cell radiosensitizers. Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med. 48, 127-138 (1985).
124. Graeber, T. G. et al. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature 379, 88-91 (1996).
125. Wartenberg, M. et al. Regulation of the multidrug resistance transporter P-glycoprotein in multicellular tumor spheroids by hypoxia-inducible factor (HIF-1) and reactive oxygen species. FASEB J. 17, 503-505 (2003).
126. Comerford, K. M. et al. Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance (MDR1) gene. Cancer Res. 62, 3387-3394 (2002).
127. Koshiji, M. et al. HIF-1α induces genetic instability by transcriptionally downregulating MutSα expression. Mol. Cell 17, 793-803 (2005).
128. Erler, J. T. et al. Lysyl oxidase is essential for hypoxia-induced metastasis. Nature 440, 1222-1226 (2006).
129. Staller, P. et al. Chemokine receptor CXCR4 downregulated by von Hippel-Lindau tumour suppressor pVHL. Nature 425, 307-311 (2003).
130. Pennacchietti, S. et al. Hypoxia promotes invasive growth by transcriptional activation of the met protooncogene. Cancer Cell 3, 347-361 (2003).
131. Moeller, B. J., Richardson, R. A. & Dewhirst, M. W. Hypoxia and radiotherapy: opportunities for improved outcomes in cancer treatment. Cancer Metastasis Rev. 26, 241-248 (2007).
132. Fujibayashi, Y. et al. Copper-62-ATSM: a new hypoxia imaging agent with high membrane permeability and low redox potential. J. Nucl. Med. 38, 1155-1160 (1997).
133. Evans, S. M. et al. Noninvasive detection of tumor hypoxia using the 2-nitroimidazole [18F]EF1. J. Nucl. Med. 41, 327-336 (2000).
134. Rasey, J. S. et al. Characterization of radiolabeled fluoromisonidazole as a probe for hypoxic cells. Radiat. Res. 111, 292-304 (1987).
135. Majumder, P. K. et al. mTOR inhibition reverses Akt-dependent prostate intraepithelial neoplasia through regulation of apoptotic and HIF-1-dependent pathways. Nature Med. 10, 594-601 (2004).
136. Thomas, G. V. et al. Hypoxia-inducible factor determines sensitivity to inhibitors of mTOR in kidney cancer. Nature Med. 12, 122-127 (2006).
137. 2-independent and HSP90 inhibitor-induced degradation of HIF-1α. Mol. Cell 25, 207-217 (2007).
138. Kung, A. L. et al. Small molecule blockade of transcriptional coactivation of the hypoxia-inducible factor pathway. Cancer Cell 6, 33-43 (2004).
139. Semenza, G. L. Evaluation of HIF-1 inhibitors as anticancer agents. Drug Discov. Today 12, 853-859 (2007).
140. Ferrara, N., Hillan, K. J., Gerber, H. P. & Novotny, W. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nature Rev. Drug Discov. 3, 391-400 (2004).
141. Hurwitz, H. et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N. Engl. J. Med. 350, 2335-2342 (2004).
142. Escudier, B. et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N. Engl. J. Med. 356, 125-134 (2007).
143. Ellis, L. M. & Hicklin, D. J. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nature Rev. Cancer (2008).
144. Paez, J. G. et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304, 1497-1500 (2004).
145. Lynch, T. J. et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 350, 2129-2139 (2004).
146. Kulshreshtha, R., Davuluri, R. V., Calin, G. A. & Ivan, M. A microRNA component of the hypoxic response. Cell Death Differ. 15, 667-671 (2008).
147. Percy, M. J. et al. Novel exon 12 mutations in the HIF2A gene associated with erythrocytosis. Blood 111, 5400-5402 (2008).
148. Percy, M. J. et al. A gain-of-function mutation in the HIF2A gene in familial erythrocytosis. N. Engl. J. Med. 358, 162-168 (2008).
149. Hickey, M. M., Lam, J. C., Bezman, N. A., Rathmell, W. K. & Simon, M. C. von Hippel-Lindau mutation in mice recapitulates Chuvash polycythemia via hypoxia-inducible factor-2α signaling and splenic erythropoiesis. J. Clin. Invest. 117, 3879-3889 (2007).
150. Jurgensen, J. S. et al. Persistent induction of HIF-1α and -2α in cardiomyocytes and stromal cells of ischemic myocardium. FASEB J. 18, 1415-1417 (2004).
151. Loor, G. & Schumacker, P. T. Role of hypoxia-inducible factor in cell survival during myocardial ischemia-reperfusion. Cell Death Differ. 15, 686-690 (2008).
152. Kido, M. et al. Hypoxia-inducible factor 1-α reduces infarction and attenuates progression of cardiac dysfunction after myocardial infarction in the mouse. J. Am. Coll. Cardiol 46, 2116-2124 (2005).
153. Yu, A. Y. et al. Impaired physiological responses to chronic hypoxia in mice partially deficient for hypoxia-inducible factor 1α. J. Clin. Invest. 103, 691-696 (1999).
154. Brusselmans, K. et al. Heterozygous deficiency of hypoxia-inducible factor-2alpha protects mice against pulmonary hypertension and right ventricular dysfunction during prolonged hypoxia. J. Clin. Invest. 111, 1519-1527 (2003).
155. Cramer, T. et al. HIF-1α is essential for myeloid cell-mediated inflammation. Cell 112, 645-657 (2003).
156. Karhausen, J. et al. Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis. J. Clin. Invest. 114, 1098-1106 (2004).