REFERENCES
1. Moeller BJ, Richardson RA, Dewhirst MW. Hypoxia and radiotherapy: opportunities for improved outcomes in cancer treatment. Cancer Metastasis Rev. 2007;26:241-8.
2. Rohwer N, Cramer T. Hypoxia-mediated drug resistance: novel insights on the functional interaction of HIFs and cell death pathways. Drug Resist Updat. 2011;14:191-201.
3. McKeown SR. Defining normoxia, physoxia and hypoxia in tumours-implications for treatment response. Br J Radiol. 2014;87:20130676.
4. Balamurugan K. HIF-1 at the crossroads of hypoxia, inflammation, and cancer. Int J Cancer. 2016;138:1058-66.
5. Bruick RK, McKnight SL. A conserved family of prolyl-4-hydroxylases that modify HIF. Science. 2001;294:1337-40.
6. Tarrado-Castellarnau M, de Atauri P, Cascante M. Oncogenic regulation of tumor metabolic reprogramming. Oncotarget. 2016;7:62726-53.
7. Luo F, Shi J, Shi Q, Xu X, Xia Y, He X. Mitogen-activated protein kinases and hypoxic/ischemic nephropathy. Cell Physiol Biochem. 2016;39:1051-67.
8. D'Ignazio L, Bandarra D, Rocha S. NF-kappaB and HIF crosstalk in immune responses. FEBS J. 2016;283:413-24.
9. Muz B, de la Puente P, Azab F, Azab AK. The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia (Auckl). 2015;3:83-92.
11. Vaupel P, Hockel M, Mayer A. Detection and characterization of tumor hypoxia using pO2 histography. Antioxid Redox Signal. 2007;9:1221-35.
12. Rudolfsson SH, Bergh A. Hypoxia drives prostate tumour progression and impairs the effectiveness of therapy, but can also promote cell death and serve as a therapeutic target. Expert Opin Ther Targets. 2009;13:219-25.
13. Tsai YP, Wu KJ. Hypoxia-regulated target genes implicated in tumor metastasis. J Biomed Sci. 2012;19:102.
14. Taiakina D, Dal Pra A, Bristow RG. Intratumoral hypoxia as the genesis of genetic instability and clinical prognosis in prostate cancer. Adv Exp Med Biol. 2014;772:189-204.
15. Byrne NM, Nesbitt H, Ming L, McKeown SR, Worthington J, McKenna DJ. Androgen deprivation in LNCaP prostate tumour xenografts induces vascular changes and hypoxic stress, resulting in promotion of epithelial-to-mesenchymal transition. Br J Cancer. 2016;114:659-68.
16. Li MC, Wang YX, Luo Y, Zhao JH, Li Q, Zhang J, Jiang YG. Hypoxia inducible factor-1 alpha-dependent epithelial to mesenchymal transition under hypoxic conditions in prostate cancer cells. Oncol Rep. 2016;36:521-7.
17. Butterworth KT, McCarthy HO, Devlin A, Ming L, Robson T, McKeown SR, Worthington J. Hypoxia selects for androgen independent LNCaP cells with a more malignant geno- and phenotype. Int J Cancer. 2008;123:760-8.
18. Graeber TG, Osmanian C, Jacks T, Housman DE, Koch CJ, Lowe SW, Giaccia AJ. Hypoxia-mediated selection of cells with diminished apoptotic potential in solid tumours. Nature. 1996;379:88-91.
19. Ranasinghe WKB, Baldwin GS, Bolton D, Shulkes A, Ischia J, Patel O. HIF1 alpha expression under normoxia in prostate cancer-which pathways to target? J Urol. 2015;193:763-70.
20. Gray LH, Conger AD, Ebert M, Hornsey S, Scott OC. The concentration of oxygen dissolved in tissues at the time of irradiation as a factor in radiotherapy. Br J Radiol. 1953;26:638-48.
21. King HW, Michael MZ, Gleadle JM. Hypoxic enhancement of exosome release by breast cancer cells. BMC Cancer. 2012;12:421.
22. Turaka A, Buyyounouski MK, Hanlon AL, Horwitz EM, Greenberg RE, Movsas B. Hypoxic prostate/muscle PO2 ratio predicts for outcome in patients with localized prostate cancer: long-term results. Int J Radiat Oncol Biol Phys. 2012;82:E433-9.
23. Zhang W, Zhou X, Yao Q, Liu Y, Zhang H, Dong Z. HIF-1-mediated production of exosomes during hypoxia is protective in renal tubular cells. Am J Physiol Renal Physiol. 2017;313:F906-F13.
24. Thery C, Zitvogel L, Amigorena S. Exosomes: composition, biogenesis and function. Nat Rev Immunol. 2002;2:569-79.
25. Ramteke A, Ting H, Agarwal C, Mateen S, Somasagara R, Hussain A, Graner M, Frederick B, Agarwal R, Deep G. Exosomes secreted under hypoxia enhance invasiveness and stemness of prostate cancer cells by targeting adherens junction molecules. Mol Carcinog. 2015;54:554-65.
26. Deep G, Panigrahi GK. Hypoxia-induced signaling promotes prostate cancer progression: exosomes role as messenger of hypoxic response in tumor microenvironment. Crit Rev Oncog. 2015;20:419-34.
27. Fraga A, Ribeiro R, Prnicipe P, Lopes C, Medeiros R. Hypoxia and prostate cancer aggressiveness: a tale with many endings. Clin Genitourin Cancer. 2015;13:295-301.
28. Stewart GD, Ross JA, McLaren DB, Parker CC, Habib FK, Riddick ACP. The relevance of a hypoxic tumour microenvironment in prostate cancer. BJU Int. 2010;105:8-13.
29. Paolicchi E, Gemignani F, Krstic-Demonacos M, Dedhar S, Mutti L, Landi S. Targeting hypoxic response for cancer therapy. Oncotarget. 2016;7:13464-78.
30. Wigerup C, Pahlman S, Bexell D. Therapeutic targeting of hypoxia and hypoxia-inducible factors in cancer. Pharmacol Ther. 2016;164:152-69.
31. Hunter FW, Wouters BG, Wilson WR. Hypoxia-activated prodrugs: paths forward in the era of personalised medicine. Br J Cancer. 2016;114:1071-7.
32. Phillips RM. Targeting the hypoxic fraction of tumours using hypoxia-activated prodrugs. Cancer Chemother Pharmacol. 2016;77:441-57.
34. Bennewith KL, Dedhar S. Targeting hypoxic tumour cells to overcome metastasis. BMC Cancer. 2011;11:504.
35. Albertella MR, Loadman PM, Jones PH, Phillips RM, Rarnpling R, Burnet N, Alcock C, Anthoney A, Vjaters E, Dunk CR, Harris PA, Wong A, Lalani AS, Twelves CJ. Hypoxia-selective targeting by the bioreductive prodrug AQ4N in patients with solid tumors: results of a phase I study. Clin Cancer Res. 2008;14:1096-104.
36. Patterson LH. Rationale for the use of aliphatic N-Oxides of cytotoxic anthraquinones as prodrug DNA-binding agents - a new class of bioreductive agent. Cancer Metastasis Rev. 1993;12:119-34.
37. Raleigh SM, Wanogho E, Burke MD, McKeown SR, Patterson LH. Involvement of human cytochromes P450 (CYP) in the reductive metabolism of AQ4N, a hypoxia activated anthraquinone di-N-oxide prodrug. Int J Radiat Oncol Biol Phys. 1998;42:763-7.
38. McCarthy HO, Yakkundi A, McErlane V, Hughes CM, Keilty G, Murray M, Patterson LH, Hirst DG, McKeown SR, Robson T. Bioreductive GDEPT using cytochrome P450 3A4 in combination with AQ4N. Cancer Gene Ther. 2003;10:40-8.
39. McErlane V, Yakkundi A, McCarthy HO, Hughes CM, Patterson LH, Hirst DG, Robson T, McKeown SR. A cytochrome P4502B6 meditated gene therapy strategy to enhance the effects of radiation or cyclophosphamide when combined with the bioreductive drug AQ4N. J Gene Med. 2005;7:851-9.
40. Yakkundi A, McErlane V, Murray M, McCarthy HO, Ward C, Hughes CM, Patterson LH, Hirst DG, McKeown SR, Robson T. Tumor-selective drug activation: a GDEPT approach utilizing cytochrome P450 1A1 and AQ4N. Cancer Gene Ther. 2006;13:598-605.
41. Nishida CR, Lee M, de Montellano PRO. Efficient hypoxic activation of the anticancer agent AQ4N by CYP2S1 and CYP2W1. Mol Pharmacol. 2010;78:497-502.
42. Saggar JK, Tannock IF. Activity of the hypoxia- activated pro- drug TH-302 in hypoxic and perivascular regions of solid tumors and its potential to enhance therapeutic effects of chemotherapy. Int J Cancer. 2014;134:2726-34.
43. DiSilvestro PA, Ali S, Craighead PS, Lucci JA, Lee YC, Cohn DE, Spirtos NM, Tewari KS, Muller C, Gajewski WH, Steinhoff MM, Monk BJ. Phase III randomized trial of weekly cisplatin and irradiation versus cisplatin and tirapazamine and irradiation in Stages IB2, IIA, IIB, IIIB, and IVA cervical carcinoma limited to the pelvis: a gynecologic oncology group study. J Clin Oncol. 2014;32:458-U81.
44. Steward WP, Middleton M, Benghiat A, Loadman PM, Hayward C, Waller S, Ford S, Halbert G, Patterson LH, Talbot D. The use of pharmacokinetic and pharmacodynamic end points to determine the dose of AQ4N, a novel hypoxic cell cytotoxin, given with fractionated radiotherapy in a phase I study. Ann Oncol. 2007;18:1098-103.
45. Wu M, Wang X, McGregor N, Pienta KJ, Zhang J. Dynamic regulation of Rad51 by E2F1 and p53 in prostate cancer cells upon drug-induced DNA damage under hypoxia. Mol Pharmacol. 2014;85:866-76.
46. Gu Y, Patterson AV, Atwell GJ, Chernikova SB, Brown JM, Thompson LH, Wilson WR. Roles of DNA repair and reductase activity in the cytotoxicity of the hypoxia-activated dinitrobenzamide mustard PR-104A. Mol Cancer Ther. 2009;8:1714-23.
47. Evans JW, Chernikova SB, Kachnic LA, Banath JP, Sordet O, Delahoussaye YM, Treszezamsky A, Chon BH, Feng Z, Gu Y, Wilson WR, Pommier Y, Olive PL, Powell SN, Brown JM. Homologous recombination is the principal pathway for the repair of DNA damage induced by tirapazamine in mammalian cells. Cancer Res. 2008;68:257-65.
48. Olcina M, Lecane PS, Hammond EM. Targeting hypoxic cells through the DNA damage response. Clin Cancer Res. 2010;16:5624-9.
49. Lindquist KE, Cran JD, Kordic K, Kyle AH, Minchinton AI. Sensitization of hypoxic cells to ionising radiation by a hypoxia activated inhibitor of DNA dependent protein kinase. EJC Supplements. 2010;8:161-2.
50. Gani C, Coackley C, Kumareswaran R, Schutze C, Krause M, Zafarana G, Bristow RG. In vivo studies of the PARP inhibitor, AZD-2281, in combination with fractionated radiotherapy: an exploration of the therapeutic ratio. Radiother Oncol. 2015;116:486-94.
51. Jiang Y, Verbiest T, Devery AM, Bokobza SM, Weber AM, Leszczynska KB, Hammond EM, Ryan AJ. Hypoxia potentiates the radiation-sensitizing effect of olaparib in human non-small cell lung cancer xenografts by contextual synthetic lethality. Int J Radiat Oncol Biol Phys. 2016;95:772-81.
52. Mistry IN, Thomas M, Calder EDD, Conway SJ, Hammond EM. Clinical advances of hypoxia-activated prodrugs in combination with radiation therapy. Int J Radiat Oncol Biol Phys. 2017;98:1183-96.
53. Barreto-Andrade JC, Efimova EV, Mauceri HJ, Beckett MA, Sutton HG, Darga TE, Vokes EE, Posner MC, Kron SJ, Weichselbaum RR. Response of human prostate cancer cells and tumors to combining PARP inhibition with ionizing radiation. Mol Cancer Ther. 2011;10:1185-93.
54. Patterson LH. Bioreductively activated antitumor N-oxides: the case of AQ4N, a unique approach to hypoxia-activated cancer chemotherapy. Drug Metab Rev. 2002;34:581-92.
55. Nesbitt H, Byrne NM, Williams SN, Ming L, Worthington J, Errington RJ, Patterson LH, Smith PJ, McKeown SR, McKenna DJ. Targeting hypoxic prostate tumors using the novel hypoxia-activated prodrug OCT1002 inhibits expression of genes associated with malignant progression. Clin Cancer Res. 2017;23:1797-808.
56. Pors K, Shnyder SD, Teesdale-Spittle PH, Hartley JA, Zloh M, Searcey M, Patterson LH. Synthesis of DNA-directed pyrrolidinyl and piperidinyl confined alkylating chloroalkylaminoanthraquinones: Potential for development of tumor-selective N-oxides. J Med Chem. 2006;49:7013-23.
57. Ming L, Byrne NM, Camac SN, Mitchell CA, Ward C, Waugh DJ, McKeown SR, Worthington J. Androgen deprivation results in time-dependent hypoxia in LNCaP prostate tumours: Informed scheduling of the bioreductive drug AQ4N improves treatment response. Int J Cancer. 2013;132:1323-32.
58. Wade D. Deuterium isotope effects on noncovalent interactions between molecules. Chem Biol Interact. 1999;117:191-217.
59. Alonzi R, Padhani AR, Taylor NJ, Collins DJ, D'Arcy JA, Stirling JJ, Saunders MI, Hoskin PJ. Antivascular effects of neoadjuvant androgen deprivation for prostate cancer: an in vivo human study using susceptibility and relaxivity dynamic MRI. Int J Radiat Oncol Biol Phys. 2011;80:721-7.
60. Milosevic M, Chung P, Parker C, Bristow R, Toi A, Panzarella T, Warde P, Catton C, Menard C, Bayley A, Gospodarowicz M, Hill R. Androgen withdrawal in patients reduces prostate cancer hypoxia: Implications for disease progression and radiation response. Cancer Res. 2007;67:6022-5.
61. Sweeney CJ, Chen YH, Carducci M, Liu G, Jarrard DF, Eisenberger M, Wong YN, Hahn N, Kohli M, Cooney MM, Dreicer R, Vogelzang NJ, Picus J, Shevrin D, Hussain M, Garcia JA, DiPaola RS. Chemohormonal therapy in metastatic hormone-sensitive prostate cancer. N Engl J Med. 2015;373:737-46.
62. James ND, Sydes MR, Clarke NW, Mason MD, Dearnaley DP, Spears MR, Ritchie AWS, Parker CC, Russell JM, Attard G, de Bono J, Cross W, Jones RJ, Thalmann G, Amos C, Matheson D, Millman R, Alzouebi M, Beesley S, Birtle AJ, Brock S, Cathomas R, Chakraborti P, Chowdhury S, Cook A, Elliott T, Gale J, Gibbs S, Graham JD, Hetherington J, Hughes R, Laing R, McKinna F, McLaren DB, O'Sullivan JM, Parikh O, Peedell C, Protheroe A, Robinson AJ, Srihari N, Srinivasan R, Staffurth J, Sundar S, Tolan S, Tsang D, Wagstaff J, Parmar MK; STAMPEDE investigators. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet. 2016;387:1163-77.
63. Li F, Joergensen JT, Hansen AE, Kjaer A. Kinetic modeling in PET imaging of hypoxia. Am J Nucl Med Mol Imaging. 2014;4:490-506.
64. White NS, Errington RJ. Fluorescence techniques for drug delivery research: theory and practice. Adv Drug Deliv Rev. 2005;57:17-42.
65. Errington RJ, Ameer-Beg SM, Vojnovic B, Patterson LH, Zloh M, Smith PJ. Advanced microscopy solutions for monitoring the kinetics and dynamics of drug-DNA targeting in living cells. Adv Drug Deliv Rev. 2005;57:153-67.
66. Feng L, Cheng L, Dong Z, Tao D, Barnhart TE, Cai W, Chen M, Liu Z. Theranostic liposomes with hypoxia-activated prodrug to effectively destruct hypoxic tumors post-photodynamic therapy. ACS Nano. 2017;11:927-37.
67. Williams KJ, Albertella MR, Fitzpatrick B, Loadman PM, Shnyder SD, Chinje EC, Telfer BA, Dunk CR, Harris PA, Stratford IJ. In vivo activation of the hypoxia-targeted cytotoxin AQ4N in human tumor xenografts. Mol Cancer Ther. 2009;8:3266-75.
68. Yang KS, Kohler RH, Landon M, Giedt R, Weissleder R. Single cell resolution in vivo imaging of DNA damage following PARP inhibition. Sci Rep. 2015;5:10129.
69. Polanski R, Vincent J, Polanska UM, Petreus T, Tang EK. Caspase-8 activation by TRAIL monotherapy predicts responses to IAPi and TRAIL combination treatment in breast cancer cell lines. Cell Death Dis. 2015;6:e1893.
70. Fricke T, Mart RJ, Watkins CL, Wiltshire M, Errington RJ, Smith PJ, Jones AT, Allemann RK. Chemical synthesis of cell-permeable apoptotic peptides from in vivo produced proteins. Bioconjug Chem. 2011;22:1763-7.
71. Mart RJ, Errington RJ, Watkins CL, Chappell SC, Wiltshire M, Jones AT, Smith PJ, Allemann RK. BH3 helix-derived biophotonic nanoswitches regulate cytochrome c release in permeabilised cells. Mol Biosyst. 2013;9:2597-603.
72. Del Gaizo Moore V, Letai A. BH3 profiling--measuring integrated function of the mitochondrial apoptotic pathway to predict cell fate decisions. Cancer Lett. 2013;332:202-5.
73. Abeshouse A, Ahn J, Akbani R, Ally A, Amin S, Andry CD, Annala M, Aprikian A, Armenia J, Arora A, Auman JT, Balasundaram M, Balu S, Barbieri CE, Bauer T, Benz CC, Bergeron A, Beroukhim R, Berrios M, Bivol A, Bodenheimer T, Boice L, Bootwalla MS, dos Reis RB, Boutros PC, Bowen J, Bowlby R, Boyd J, Bradley RK, Breggia A, Brimo F, Bristow CA, Brooks D, Broom BM, Bryce AH, Bubley G, Burks E, Butterfield YSN, Button M, Canes D, Carlotti CG, Carlsen R, Carmel M, Carroll PR, Carter SL, Cartun R, Carver BS, Chan JM, Chang MT, Chen Y, Cherniack AD, Chevalier S, Chin L, Cho J, Chu A, Chuah E, Chudamani S, Cibulskis K, Ciriello G, Clarke A, Cooperberg MR, Corcoran NM, Costello AJ, Cowan J, Crain D, Curley E, David K, Demchok JA, Demichelis F, Dhalla N, Dhir R, Doueik A, Drake B, Dvinge H, Dyakova N, Felau I, Ferguson ML, Frazer S, Freedland S, Fu Y, Gabriel SB, Gao JJ, Gardner J, Gastier-Foster JM, Gehlenborg N, Gerken M, Gerstein MB, Getz G, Godwin AK, Gopalan A, Graefen M, Graim K, Gribbin T, Guin R, Gupta M, Hadjipanayis A, Haider S, Hamel L, Hayes DN, Heiman DI, Hess J, Hoadley KA, Holbrook AH, Holt RA, Holway A, Hovens CM, Hoyle AP, Huang M, Hutter CM, Ittmann M, Iype L, Jefferys SR, Jones CD, Jones SJM, Juhl H, Kahles A, Kane CJ, Kasaian K, Kerger M, Khurana E, Kim J, Klein RJ, Kucherlapati R, Lacombe L, Ladanyi M, Lai PH, Laird PW, Lander ES, Latour M, Lawrence MS, Lau K, LeBien T, Lee D, Lee S, Lehmann KV, Leraas KM, Leshchiner I, Leung R, Libertino JA, Lichtenberg TM, Lin P, Linehan WM, Ling S, Lippman SM, Liu J, Liu W, Lochovsky L, Loda M, Logothetis C, Lolla L, Longacre T, Lu YL, Luo JH, Ma Y, Mahadeshwar HS, Mallery D, Mariamidze A, Marra MA, Mayo M, McCall S, McKercher G, Meng S, Mes-Masson AM, Merino MJ, Meyersson M, Mieczkowski PA, Mills GB, Shaw KRM, Minner S, Moinzadeh A, Moore RA, Morris S, Morrison C, Mose LE, Mungall AJ, Murray BA, Myers JB, Naresh R, Nelson J, Nelson MA, Nelson PS, Newton Y, Noble MS, Noushmehr H, Nykter M, Pantazi A, Parfenov M, Park PJ, Parker JS, Paulauskis J, Penny R, Perou CM, Piche A, Pihl T, Pinto PA, Prandi D, Protopopov A, Ramirez NC, Rao A, Rathmell WK, Ratsch G, Ren XJ, Reuter VE, Reynolds SM, Rhie SK, Rieger-Christ K, Roach J, Robertson AG, Robinson B, Rubin MA, Saad F, Sadeghi S, Saksena G, Saller C, Salner A, Sanchez-Vega F, Sander C, Sandusky G, Sauter G, Sboner A, Scardino PT, Scarlata E, Schein JE, Schlomm T, Schmidt LS, Schultz N, Schumacher SE, Seidman J, Neder L, Seth S, Sharp A, Shelton C, Shelton T, Shen H, Shen RL, Sherman M, Sheth M, Shi Y, Shih J, Shmulevich I, Simko J, Simon R, Simons JV, Sipahimalani P, Skelly T, Sofia HJ, Soloway MG, Song XZ, Sorcini A, Sougnez C, Stepa S, Stewart C, Stewart J, Stuart JM, Sullivan TB, Sun C, Sun HD, Tam A, Tan DH, Tang JB, Tarnuzzer R, Tarvin K, Taylor BS, Teebagy P, Tenggara I, Tetu B, Tewari A, Thiessen N, Thompson T, Thorne LB, Tirapelli DP, Tomlins SA, Trevisan FA, Troncoso P, True LD, Tsourlakis MC, Tyekucheva S, Van Allen E, Van den Berg DJ, Veluvolu U, Verhaak R, Vocke CD, Voet D, Wan YH, Wang QG, Wang WY, Wang ZN, Weinhold N, Weinstein JN, Weisenberger DJ, Wilkerson MD, Wise L, Witte J, Wu CC, Wu JY, Wu Y, Xu AW, Yadav SS, Yang LM, Yang LX, Yau C, Ye HH, Yena P, Zeng T, Zenklusen JC, Zhang HL, Zhang JH, Zhang JS, Zhang W, Zhong Y, Zhu K, Zmuda E, Cancer Genome Atlas Research Network. The molecular taxonomy of primary prostate cancer. Cell. 2015;163:1011-25.
74. Ciccarese C, Santoni M, Brunelli M, Buti S, Modena A, Nabissi M, Artibani W, Martignoni G, Montironi R, Tortora G, Massari F. AR-V7 and prostate cancer: the watershed for treatment selection? Cancer Treat Rev. 2016;43:27-35.
75. Buffa FM, Harris AL, West CM, Miller CJ. Large meta-analysis of multiple cancers reveals a common, compact and highly prognostic hypoxia metagene. Br J Cancer. 2010;102:428-35.
76. Winter SC, Buffa FM, Silva P, Miller C, Valentine HR, Turley H, Shah KA, Cox GJ, Corbridge RJ, Homer JJ, Musgrove B, Slevin N, Sloan P, Price P, West CML, Harris AL. Relation of a hypoxia metagene derived from head and neck cancer to prognosis of multiple cancers. Cancer Res. 2007;67:3441-9.
77. Eustace A, Mani N, Span PN, Irlam JJ, Taylor J, Betts GN, Denley H, Miller CJ, Homer JJ, Rojas AM, Hoskin PJ, Buffa FM, Harris AL, Kaanders JH, West CM. A 26-gene hypoxia signature predicts benefit from hypoxia-modifying therapy in laryngeal cancer but not bladder cancer. Clin Cancer Res. 2013;19:4879-88.
78. Lalonde E, Ishkanian AS, Sykes J, Fraser M, Ross-Adams H, Erho N, Dunning MJ, Halim S, Lamb AD, Moon NC, Zafarana G, Warren AY, Meng XY, Thoms J, Grzadkowski MR, Berlin A, Have CL, Ramnarine VR, Yao CQ, Malloff CA, Lam LL, Xie HL, Harding NJ, Mak DYF, Chu KC, Chong LC, Sendorek DH, P'ng C, Collins CC, Squire JA, Jurisica I, Cooper C, Eeles R, Pintilie M, Dal Pra A, Davicioni E, Lam WL, Milosevic M, Neal DE, van der Kwast T, Boutros PC, Bristow RG. Tumour genomic and microenvironmental heterogeneity for integrated prediction of 5-year biochemical recurrence of prostate cancer: a retrospective cohort study. Lancet Oncol. 2014;15:1521-32.
79. Ragnum HB, Vlatkovic L, Lie AK, Axcrona K, Julin CH, Frikstad KM, Hole KH, Seierstad T, Lyng H. The tumour hypoxia marker pimonidazole reflects a transcriptional programme associated with aggressive prostate cancer. Br J Cancer. 2015;112:382-90.
80. Luu HN, Lin HY, Sorensen KD, Ogunwobi OO, Kumar N, Chornokur G, Phelan C, Jones D, Kidd L, Batra J, Yamoah K, Berglund A, Rounbehler RJ, Yang M, Lee SH, Kang N, Kim SJ, Park JY, Di Pietro G. miRNAs associated with prostate cancer risk and progression. BMC Urol. 2017;17.
81. Lynch SM, O'Neill KM, McKenna MM, Walsh CP, McKenna DJ. Regulation of miR-200c and miR-141 by methylation in prostate cancer. Prostate. 2016;76:1146-59.
82. Dang K, Myers KA. The role of hypoxia-induced miR-210 in cancer progression. Int J Mol Sci. 2015;16:6353-72.
83. Huang X, Le QT, Giaccia AJ. MiR-210-micromanager of the hypoxia pathway. Trends Mol Med. 2010;16:230-7.
84. Taddei ML, Cavallini L, Comito G, Giannoni E, Folini M, Marini A, Gandellini P, Morandi A, Pintus G, Raspollini MR, Zaffaroni N, Chiarugi P. Senescent stroma promotes prostate cancer progression: the role of miR-210. Mol Oncol. 2014;8:1729-46.
85. Haldrup C, Kosaka N, Ochiya T, Borre M, Hoyer S, Orntoft TF, Sorensen KD. Profiling of circulating microRNAs for prostate cancer biomarker discovery. Drug Deliv Transl Res. 2014;4:19-30.
86. Cheng HH, Mitchell PS, Kroh EM, Dowell AE, Chery L, Siddiqui J, Nelson PS, Vessella RL, Knudsen BS, Chinnaiyan AM, Pienta KJ, Morrissey C, Tewari M. Circulating microRNA profiling identifies a subset of metastatic prostate cancer patients with evidence of cancer-associated hypoxia. PLoS One. 2013;8:e69239.
87. Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, Rodrigues DN, Robinson D, Omlin A, Tunariu N, Boysen G, Porta N, Flohr P, Gillman A, Figueiredo I, Paulding C, Seed G, Jain S, Ralph C, Protheroe A, Hussain S, Jones R, Elliott T, McGovern U, Bianchini D, Goodall J, Zafeiriou Z, Williamson CT, Ferraldeschi R, Riisnaes R, Ebbs B, Fowler G, Roda D, Yuan W, Wu YM, Cao X, Brough R, Pemberton H, A'Hern R, Swain A, Kunju LP, Eeles R, Attard G, Lord CJ, Ashworth A, Rubin MA, Knudsen KE, Feng FY, Chinnaiyan AM, Hall E, de Bono JS. DNA-repair defects and olaparib in metastatic prostate cancer. N Engl J Med. 2015;373:1697-708.
88. Nordsmark M, Bentzen SM, Overgaard J. Measurement of human tumour oxygenation status by a polarographic needle electrode. An analysis of inter- and intratumour heterogeneity. Acta Oncol. 1994;33:383-9.
89. Becker A, Hansgen G, Bloching M, Weigel C, Lautenschlager C, Dunst J. Oxygenation of squamous cell carcinoma of the head and neck: comparison of primary tumors, neck node metastases, and normal tissue. Int J Radiat Oncol Biol Phys. 1998;42:35-41.
90. Le QT, Kovacs MS, Dorie MJ, Koong A, Terris DJ, Pinto HA, Goffinet DR, Nowels K, Bloch D, Brown JM. Comparison of the comet assay and the oxygen microelectrode for measuring tumor oxygenation in head-and-neck cancer patients. Int J Radiat Oncol Biol Phys. 2003;56:375-83.
91. Falk SJ, Ward R, Bleehen NM. The influence of carbogen breathing on tumour tissue oxygenation in man evaluated by computerised p02 histography. Br J Cancer. 1992;66:919-24.
92. Le QT, Chen E, Salim A, Cao H, Kong CS, Whyte R, Donington J, Cannon W, Wakelee H, Tibshirani R, Mitchell JD, Richardson D, O'Byrne KJ, Koong AC, Giaccia AJ. An evaluation of tumor oxygenation and gene expression in patients with early stage non-small cell lung cancers. Clin Cancer Res. 2006;12:1507-14.
93. Vaupel P, Mayer A, Briest S, Hockel M. Oxygenation gain factor: a novel parameter characterizing the association between hemoglobin level and the oxygenation status of breast cancers. Cancer Res. 2003;63:7634-7.
94. Koong AC, Mehta VK, Le QT, Fisher GA, Terris DJ, Brown JM, Bastidas AJ, Vierra M. Pancreatic tumors show high levels of hypoxia. Int J Radiat Oncol Biol Phys. 2000;48:919-22.
95. Graffman S, Bjork P, Ederoth P, Ihse I. Polarographic pO2 measurements of intra-abdominal adenocarcinoma in connection with intraoperative radiotherapy before and after change of oxygen concentration of anaesthetic gases. Acta Oncol. 2001;40:105-7.
96. Movsas B, Chapman JD, Hanlon AL, Horwitz EM, Pinover WH, Greenberg RE, Stobbe C, Hanks GE. Hypoxia in human prostate carcinoma: an Eppendorf PO2 study. Am J Clin Oncol. 2001;24:458-61.
97. Parker C, Milosevic M, Toi A, Sweet J, Panzarella T, Bristow R, Catton C, Catton P, Crook J, Gospodarowicz M, McLean M, Warde P, Hill RP. Polarographic electrode study of tumor oxygenation in clinically localized prostate cancer. Int J Radiat Oncol Biol Phys. 2004;58:750-7.
98. Movsas B, Chapman JD, Horwitz EM, Pinover WH, Greenberg RE, Hanlon AL, Iyer R, Hanks GE. Hypoxic regions exist in human prostate carcinoma. Urology. 1999;53:11-8.
99. Lartigau E, Randrianarivelo H, Avril MF, Margulis A, Spatz A, Eschwege F, Guichard M. Intratumoral oxygen tension in metastatic melanoma. Melanoma Res. 1997;7:400-6.
100. Kallinowski FBH. Can the oxygenation status of rectal carcinomas be improved by hypoxia? Tumor oxygenation. 1995:291-6.
101. Mattern J, Kallinowski F, Herfarth C, Volm M. Association of resistance-related protein expression with poor vascularization and low levels of oxygen in human rectal cancer. Int J Cancer. 1996;67:20-3.
102. von Pawel J, von Roemeling R, Gatzemeier U, Boyer M, Elisson LO, Clark P, Talbot D, Rey A, Butler TW, Hirsh V, Olver I, Bergman B, Ayoub J, Richrdson G, Dunlop D, Arcenas A, Vescio R, Viallet J, Treat J. Tirapazamine plus cisplatin versus cisplatin in advanced non-small-cell lung cancer: a report of the international CATAPULT I study group. J Clin Oncol. 2000;18:1351-9.
103. Marcu L, Olver I. Tirapazamine: from bench to clinical trials. Curr Clin Pharmacol. 2006;1:71-9.
104. Phillips RM, Hendriks HR, Peters GJ, Grp E-PMM. EO9 (Apaziquone): from the clinic to the laboratory and back again. Br J Pharmacol. 2013;168:11-8.
105. Hendricksen K, Cornel EB, de Reijke TM, Arentsen HC, Chawla S, Witjes JA. Phase 2 study of adjuvant intravesical instillations of apaziquone for high risk nonmuscle invasive bladder cancer. J Urol. 2012;187:1195-9.
106. Meng FY, Evans JW, Bhupathi D, Banica M, Lan L, Lorente G, Duan JX, Cai XH, Mowday AM, Guise CP, Maroz A, Anderson RF, Patterson AV, Stachelek GC, Glazer PM, Matteucci MD, Hart CP. Molecular and cellular pharmacology of the hypoxia-activated prodrug TH-302. Mol Cancer Ther. 2012;11:740-51.
107. Riedel RF, Meadows KL, Lee PH, Morse MA, Uronis HE, Blobe GC, George DJ, Crawford J, Niedzwiecki D, Rushing CN, Arrowood CC, Hurwitz HI. Phase I study of pazopanib plus TH-302 in advanced solid tumors. Cancer Chemother Pharmacol. 2017;79:611-9.
108. Badar T, Handisides DR, Benito JM, Richie MA, Borthakur G, Jabbour E, Harutyunyan K, Konoplev S, Faderl S, Kroll S, Andreeff M, Pearce T, Kantarjian HM, Cortes JE, Thomas DA, Konopleva M. Phase I study of evofosfamide, an investigational hypoxia-activated prodrug, in patients with advanced leukemia. Am J Hematol. 2016;91:800-5.
109. Patterson AV, Silva S, Guise C, Bull M, Abbattista M, Hsu A, Sun JD, Hart CP, Pearce TE, Smaill JB. TH-4000, a hypoxia-activated EGFR/Her2 inhibitor to treat EGFR-TKI resistant T790M-negative NSCLC. J Clin Oncol. 2015;33:e13548.
110. Guise CP, Mowday AM, Ashoorzadeh A, Yuan R, Lin WH, Wu DH, Smaill JB, Patterson AV, Ding K. Bioreductive prodrugs as cancer therapeutics: targeting tumor hypoxia. Chin J Cancer. 2014;33:80-6.
111. McKeage MJ, Jameson MB, Ramanathan RK, Rajendran J, Gu YC, Wilson WR, Melink TJ, Tchekmedyian NS. PR-104 a bioreductive pre-prodrug combined with gemcitabine or docetaxel in a phase Ib study of patients with advanced solid tumours. BMC Cancer. 2012;12:496.
112. Haffty BG, Wilson LD, Son YH, Cho EI, Papac RJ, Fischer DB, Rockwell S, Sartorelli AC, Ross DA, Sasaki CT, Fischer JJ. Concurrent chemo-radiotherapy with mitomycin C compared with porfiromycin in squamous cell cancer of the head and neck: final results of a randomized clinical trial. Int J Radiat Oncol Biol Phys. 2005;61:119-28.
113. Panettiere FJ, Talley RW, Torres J, Lane M. Porfiromycin in management of epidermoid and transitional cell-cancer - phase II study. Cancer Treat Rep. 1976;60:907-11.
