The role of bystander effects in the antitumor activity of the hypoxia-activated prodrug PR-104

Frontiers in Oncology

Volumn 3 OCT, Issue , 2013, Pages

  Foehrenbacher, Annika ^a   Patel, Kashyap ^a   Abbattista, Maria R ^a   Guise, Chris P ^a   Secomb, Timothy W ^b   Wilson, William R ^a   Hicks, Kevin O ^a  

^a UNIVERSITY OF AUCKLAND   (New Zealand)

^b UNIVERSITY OF ARIZONA COLLEGE OF MEDICINE   (United States)

Author keywords

Anticancer prodrugs; Bystander effect; Extravascular drug transport; Hypoxia activated prodrugs; Multicellular layers; NADPH:cytochrome P450 oxidoreductase; Pharmacokinetic pharmacodynamic modeling; PR 104

Indexed keywords

PR 104; PRODRUG; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; BYSTANDER EFFECT; CANCER CELL CULTURE; CELL HETEROGENEITY; CELL KILLING; CELL SUSPENSION; CONTROLLED STUDY; DIFFUSION COEFFICIENT; FEMALE; FLOW CYTOMETRY; HUMAN; HUMAN CELL; HYPOXIA; IMMUNOHISTOCHEMISTRY; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; MOUSE; NONHUMAN; NUDE MOUSE; OXYGENATION; PHARMACODYNAMICS;

EID: 84891072281     PISSN: None     EISSN: 2234943X     Source Type: Journal    
DOI: 10.3389/fonc.2013.00263     Document Type: Article

References (49)

1. Marusyk A, Almendro V, Polyak K. Intra-tumour heterogeneity: a looking glass for cancer? Nat Rev Cancer (2012) 12:323-34. doi:10.1038/nrc3261
2. Bagshawe KD. Antibody-directed enzyme prodrug therapy (ADEPT) for cancer. Expert Rev Anticancer Ther (2006) 6:1421-31. doi:10.1586/14737140.6.10.1421
3. Duarte S, Carle G, Faneca H, de Lima MC, Pierrefite-Carle V. Suicide gene therapy in cancer: where do we stand now? Cancer Lett (2012) 324:160-70. doi:10.1016/j.canlet.2012.05.023
4. Tietze LF, Schmuck K. Prodrugs for targeted tumor therapies: recent developments in ADEPT, GEPT and PMT. Curr Pharm Des (2011) 17:3527-47. doi:10.2174/138161211798194459
5. Denny WA, Wilson WR. Bioreducible mustards: a paradigm for hypoxia-selective prodrugs of diffusible cytotoxins (HPDCs). Cancer Metastasis Rev (1993) 12:135-51. doi:10.1007/BF00689806
6. Wilson WR, Hay MP. Targeting hypoxia in cancer therapy. Nat Rev Cancer (2011) 11:393-410. doi:10.1038/nrc3064
7. Wilson WR, Hicks KO, Wang J, Pruijn FB. Prodrug strategies for targeting tumour hypoxia. In: Melillo G editor. Hypoxia and Cancer: Cancer Drug Discovery and Development, Chapter 13. New York: Springer (in press). doi:10.1007/978-1-4614-9167-5_13
8. Marshall RS, Rauth AM. Oxygen and exposure kinetics as factors influencing the cytotoxicity of porfiromycin, a mitomycin C analogue, in Chinese hamster ovary cells. Cancer Res (1988) 48:5655-9.
9. Siim BG, Atwell GJ, Wilson WR. Oxygen dependence of the cytotoxicity and metabolic activation of 4-alkylamino-5-nitroquinoline bioreductive drugs. Br J Cancer (1994) 70:596-603. doi:10.1038/bjc.1994.357
10. Hicks KO, Siim BG, Pruijn FB, Wilson WR. Oxygen dependence of the metabolic activation and cytotoxicity of tirapazamine: implications for extravascular transport and activity in tumors. Radiat Res (2004) 161:656-66. doi:10.1667/RR3178
11. Meng F, Evans JW, Bhupathi D, Banica M, Lan L, Lorente G, et al. Molecular and cellular pharmacology of the hypoxia-activated prodrug TH-302. Mol Cancer Ther (2012) 11:740-51. doi:10.1158/1535-7163.MCT-11-0634
12. McKeage MJ, Jameson MB, Ramanathan RK, Rajendran J, Gu Y, Wilson WR, et al. 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. doi:10.1186/1471-2407-12-496
13. Patterson AV, Ferry DM, Edmunds SJ, Gu Y, Singleton RS, Patel K, et al. Mechanism of action and preclinical antitumor activity of the novel hypoxia-activated DNA crosslinking agent PR-104. Clin Cancer Res (2007) 13:3922-32. doi:10.1158/1078-0432.CCR-07-0478
14. Gu Y, Wilson WR. Rapid and sensitive ultra-high-pressure liquid chromatography-tandem mass spectrometry analysis of the novel anticancer agent PR-104 and its major metabolites in human plasma: application to a pharmacokinetic study. J Chromatogr B Analyt Technol Biomed Life Sci (2009) 877:3181-6. doi:10.1016/j.jchromb.2009.08.009
15. Patel K, Choy SF, Hicks KO, Melink TJ, Holford NHG, Wilson WR. A combined pharmacokinetic model for the hypoxia-targeted prodrug PR-104A in humans, dogs, rats and mice predicts species differences in clearance and toxicity. Cancer Chemother Pharmacol (2011) 67:1145-55. doi:10.1007/s00280-010-1412-z
16. Singleton RS, Guise CP, Ferry DM, Pullen SM, Dorie MJ, Brown JM, et al. DNA crosslinks in human tumor cells exposed to the prodrug PR-104A: relationships to hypoxia, bioreductive metabolism and cytotoxicity. Cancer Res (2009) 69:3884-91. doi:10.1158/0008-5472.CAN-08-4023
17. Gu Y, Patterson AV, Atwell GJ, Chernikova SB, Brown JM, Thompson LH, et al. 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. doi:10.1158/1535-7163.MCT-08-1209
18. Guise CP, Wang A, Thiel A, Bridewell D, Wilson WR, Patterson AV. Identification of human reductases that activate the dinitrobenzamide mustard prodrug PR-104A: a role for NADPH:cytochrome P450 oxidoreductase under hypoxia. Biochem Pharmacol (2007) 74:810-20. doi:10.1016/j.bcp.2007.06.014
19. Guise CP, Abbattista MR, Tipparaju SR, Lambie NK, Su J, Li D, et al. Diflavin oxidoreductases activate the bioreductive prodrug PR-104A under hypoxia. Mol Pharmacol (2012) 81:31-40. doi:10.1124/mol.111.073759
20. Hicks KO, Myint H, Patterson AV, Pruijn FB, Siim BG, Patel K, et al. Oxygen dependence and extravascular transport of hypoxia-activated prodrugs: comparison of the dinitrobenzamide mustard PR-104A and tirapazamine. Int J Radiat Oncol Biol Phys (2007) 69:560-71. doi:10.1016/j.ijrobp.2007.05.049
21. Whillans DW, Hunt JW. A rapid-mixing comparison of the mechanisms of radiosensitization by oxygen and misonidazole in CHO cells. Radiat Res (1982) 90:126-41. doi:10.2307/3575801
22. Guise CP, Abbattista M, Singleton RS, Holford SD, Connolly J, Dachs GU, et al. The bioreductive prodrug PR-104A is activated under aerobic conditions by human aldo-keto reductase 1C3. Cancer Res (2010) 70:1573-84. doi:10.1158/0008-5472.CAN-09-3237
23. Houghton PJ, Lock R, Carol H, Morton CL, Phelps D, Gorlick R, et al. Initial testing of the hypoxia activated prodrug PR-104 by the Pediatric Preclinical Testing Program. Pediatr Blood Cancer (2011) 57:443-53. doi:10.1002/pbc.22921
24. Hicks KO, Pruijn FB, Secomb TW, Hay MP, Hsu R, Brown JM, et al. Use of three-dimensional tissue cultures to model extravascular transport and predict in vivo activity of hypoxia-targeted anticancer drugs. J Natl Cancer Inst (2006) 98:1118-28. doi:10.1093/jnci/djj306
25. Hicks KO, Siim BG, Jaiswal JK, Pruijn FB, Fraser AM, Patel R, et al. Pharmacokinetic/pharmacodynamic modeling identifies SN30000 and SN29751 as tirapazamine analogues with improved tissue penetration and hypoxic cell killing in tumors. Clin Cancer Res (2010) 16:4946-57. doi:10.1158/1078-0432.CCR-10-1439
26. Wilson WR, Hicks KO, Pullen SM, Ferry DM, Helsby NA, Patterson AV. Bystander effects of bioreductive drugs: potential for exploiting pathological tumor hypoxia with dinitrobenzamide mustards. Radiat Res (2007) 167:625-36. doi:10.1667/RR0807.1
27. Cowan DS, Hicks KO, Wilson WR. Multicellular membranes as an in vitro model for extravascular diffusion in tumours. Br J Cancer Suppl (1996) 27:S28-31.
28. Secomb TW, Hsu R, Braun RD, Ross JR, Gross JF, Dewhirst MW. Theoretical simulation of oxygen transport to tumors by three-dimensional networks of microvessels. Adv Exp Med Biol (1998) 454:629-34. doi:10.1007/978-1-4615-4863-8_74
29. Secomb TW, Hsu R, Park EY, Dewhirst MW. Green's function methods for analysis of oxygen delivery to tissue by microvascular networks. Ann Biomed Eng (2004) 32:1519-29. doi:10.1114/B:ABME.0000049036.08817.44
30. Pries AR, Cornelissen AJ, Sloot AA, Hinkeldey M, Dreher MR, Hoepfner M, et al. Structural adaptation and heterogeneity of normal and tumor microvascular networks. PLoS Comput Biol (2009) 5:e1000394. doi:10.1371/journal.pcbi.1000394
31. Koch CJ. Importance of antibody concentration in the assessment of cellular hypoxia by flow cytometry: EF5 and pimonidazole. Radiat Res (2008) 169:677-88. doi:10.1667/RR1305.1
32. Tuttle SW, Maity A, Oprysko PR, Kachur AV, Ayene IS, Biaglow JE, et al. Detection of reactive oxygen species via endogenous oxidative pentose phosphate cycle activity in response to oxygen concentration. J Biol Chem (2007) 282:36790-6. doi:10.1074/jbc.M700327200
33. Gu Y, Guise CP, Patel K, Abbattista MR, Li J, Sun X, et al. Reductive metabolism of the dinitrobenzamide mustard anticancer prodrug PR-104 in mice. Cancer Chemother Pharmacol (2011) 67:543-55. doi:10.1007/s00280-010-1354-5
34. Gerlowski LE, Jain RK. Microvascular permeability of normal and neoplastic tissues. Microvasc Res (1986) 31:288-305. doi:10.1016/0026-2862(86)90018-X
35. Jain RK. Delivery of molecular and cellular medicine to solid tumors. Adv Drug Deliv Rev (2012) 64:353-65. doi:10.1016/j.addr.2012.09.011
36. Smaill JB, Patterson AV, Singleton DC. Method for the Fluorescent Detection of Nitroreductase Activity Using Nitro-Substituted Aromatic Compounds. US 2010/0173332 A1 (2010).
37. Hobbs S, Jitrapakdee S, Wallace JC. Development of a bicistronic vector driven by the human polypeptide chain elongation factor 1alpha promoter for creation of stable mammalian cell lines that express very high levels of recombinant proteins. Biochem Biophys Res Commun (1998) 252:368-72. doi:10.1006/bbrc.1998.9646
38. Ahn GO, Botting KJ, Patterson AV, Ware DC, Tercel M, Wilson WR. Radiolytic and cellular reduction of a novel hypoxia-activated cobalt(III) prodrug of a chloromethylbenzindoline DNA minor groove alkylator. Biochem Pharmacol (2006) 71:1683-94. doi:10.1016/j.bcp.2006.03.007
39. Wilson WR, Pullen SM, Hogg A, Hobbs SM, Pruijn FB, Hicks KO. In vitro and in vivo models for evaluation of GDEPT: quantifying bystander killing in cell cultures and tumors. In: Springer CJ editor. Suicide Gene Therapy: Methods and Reviews. Totowa: Humana Press (2003). p. 403-32.
40. Hicks KO, Pruijn FB, Sturman JR, Denny WA, Wilson WR. Multicellular resistance to tirapazamine is due to restricted extravascular transport: a pharmacokinetic/pharmacodynamic study in HT29 multicellular layer cultures. Cancer Res (2003) 63:5970-7.
41. Pruijn FB, Patel K, Hay MP, Wilson WR, Hicks KO. Prediction of tumour tissue diffusion coefficients of hypoxia-activated prodrugs from physicochemical parameters. Aust J Chem (2008) 61:687-93. doi:10.1071/CH08240
42. Wang J, Foehrenbacher A, Su J, Patel R, Hay MP, Hicks KO, et al. The 2-nitroimidazole EF5 is a biomarker for oxidoreductases that activate bioreductive prodrug CEN-209 under hypoxia. Clin Cancer Res (2012) 18:1684-95. doi:10.1158/1078-0432.CCR-11-2296
43. Su J, Guise CP, Wilson WR. FSL-61 is a 6-nitroquinolone fluorogenic probe for one-electron reductases in hypoxic cells. Biochem J (2013) 452:79-86. doi:10.1042/BJ20121695
44. Koch CJ, Evans SM, Lord EM. Oxygen dependence of cellular uptake of EF5 [2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide]: analysis of drug adducts by fluorescent antibodies vs bound radioactivity. Br J Cancer (1995) 72:869-74. doi:10.1038/bjc.1995.426
45. Nakamura Y, Chang CC, Mori T, Sato K, Ohtsuki K, Upham BL, et al. Augmentation of differentiation and gap junction function by kaempferol in partially differentiated colon cancer cells. Carcinogenesis (2005) 26:665-71. doi:10.1093/carcin/bgi003
46. Aasen T, Hodgins MB, Edward M, Graham SV. The relationship between connexins, gap junctions, tissue architecture and tumour invasion, as studied in a novel in vitro model of HPV-16-associated cervical cancer progression. Oncogene (2003) 22:7969-80. doi:10.1038/sj.onc.1206709
47. Ozawa S, Sugiyama Y, Mitsuhashi Y, Kobayashi T, Inaba M. Cell killing action of cell cycle phase-non-specific antitumor agents is dependent on concentration-time product. Cancer Chemother Pharmacol (1988) 21:185-90. doi:10.1007/BF00262767
48. Gu Y, Atwell GJ, Wilson WR. Metabolism and excretion of the novel bioreductive prodrug PR-104 in mice, rats, dogs and humans. Drug Metab Dispos (2010) 38:498-508. doi:10.1124/dmd.109.030973
49. Cardenas-Navia LI, Secomb TW, Dewhirst MW. Effects of fluctuating oxygenation on tirapazamine efficacy: theoretical predictions. Int J Radiat Oncol Biol Phys (2007) 67:581-6. doi:10.1016/j.ijrobp.2006.10.002