Pharmacokinetic/pharmacodynamic modeling identifies SN30000 and SN29751 as tirapazamine analogues with improved tissue penetration and hypoxic cell killing in tumors

Clinical Cancer Research

Volumn 16, Issue 20, 2010, Pages 4946-4957

  Hicks, Kevin O ^a   Siim, Bronwyn G ^a,c   Jaiswal, Jagdish K ^a   Pruijn, Frederik B ^a   Fraser, Annie M ^a,d   Patel, Rita ^a   Hogg, Alison ^a   Liyanage, H D Sarath ^a   Dorie, Mary Jo ^b   Brown, J Martin ^b   Denny, William A ^a   Hay, Michael P ^a   Wilson, William R ^a  

^a UNIVERSITY OF AUCKLAND   (New Zealand)

^b STANFORD UNIVERSITY   (United States)

^c UNIVERSITY OF OXFORD   (United Kingdom)

^d Wolters Kluwer Health   (New Zealand)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOTOXIN; OXYGEN; SN 29751; SN 30000; TIRAPAZAMINE; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER CELL CULTURE; CANCER CHEMOTHERAPY; CELL KILLING; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG PENETRATION; HYPOXIC CELL; MOUSE; NONHUMAN; PRIORITY JOURNAL; RADIATION DOSE FRACTIONATION; RAT; SCREENING; SINGLE DRUG DOSE; TUMOR; XENOGRAFT;

ALGORITHMS; ANIMALS; ANTINEOPLASTIC AGENTS; CELL HYPOXIA; HT29 CELLS; HUMANS; MALE; MICE; MICE, NUDE; MODELS, BIOLOGICAL; NEOPLASMS; OXYGEN; RADIATION-SENSITIZING AGENTS; RATS; RATS, SPRAGUE-DAWLEY; TRIAZINES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 77958060317     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-10-1439     Document Type: Article

References (50)

1. Pries AR, Cornelissen AJ, Sloot AA, et al. Structural adaptation and heterogeneity of normal and tumor microvascular networks. PLoS Computational Biology 2009;5:e1000394.
2. Wardman P. The importance of radiation chemistry to radiation and free radical biology. (The 2008 Silvanus Thompson Memorial Lecture). Br J Radiol 2009;82:89-104.
3. Lunt SJ, Chaudary N, Hill RP. The tumor microenvironment and metastatic disease. Clin Exp Metastasis 2009;26:19-34.
4. Brizel DM, Scully SP, Harrelson JM, et al. Tumor oxygenation predicts for the likelihood of distant metastases in human soft tissue sarcoma. Cancer Res 1996;56:941-3.
5. Fyles A, Milosevic M, Hedley D, et al. Tumor hypoxia has independent predictor impact only in patients with node-negative cervix cancer. J Clin Oncol 2002;20:680-7. (Pubitemid 34111374)
6. Rofstad EK, Mathiesen B, Henriksen K, Kindem K, Galappathi K. The tumor bed effect: increased metastatic dissemination from hypoxia-induced up-regulation of metastasis-promoting gene products. Cancer Res 2005;65:2387-96.
7. Kioi M, Vogel H, Schultz G, Hoffman RM, Harsh GR, Brown JM. Inhibition of vasculogenesis, but not angiogenesis, prevents the recurrence of glioblastoma after irradiation in mice. J Clin Invest 2010;120:694-705.
8. 2 histography. Antioxid Redox Signal 2007;9:1221-35.
9. Semenza GL. Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene 2010;29:625-34.
10. Rouschop KM, van den BT, Dubois L, et al. The unfolded protein response protects human tumor cells during hypoxia through regulation of the autophagy genes MAP1LC3B and ATG5. J Clin Invest 2010;120:127-41.
11. Brown JM, Wilson WR. Exploiting tumor hypoxia in cancer treatment. Nat Rev Cancer 2004;4:437-47.
12. McKeown SR, Cowen RL, Williams KJ. Bioreductive drugs: from concept to clinic. Clin Oncol 2007;19:427-42.
13. Chen Y, Hu L. Design of anticancer prodrugs for reductive activation. Med Res Rev 2009;29:29-64.
14. von Pawel J, von Roemeling R, Gatzemeier U, 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 2000;18:1351-9.
15. Rischin D, Peters L, Fisher R, 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 2005;23:79-87.
16. Rischin D, Peters LJ, O'Sullivan B, et al. Tirapazamine, cisplatin, and radiation versus cisplatin and radiation for advanced squamous cell carcinoma of the head and neck (TROG 02.02, HeadSTART): a phase III trial of the Trans-Tasman Radiation Oncology Group. J Clin Oncol 2010, doi: 10.1200/JCO.2009.27.4449.
17. Peters LJ, O'Sullivan B, Giralt J, et al. Critical impact of radiotherapy protocol compliance and quality in the treatment of advanced head and neck cancer: results from TROG 02.02. J Clin Oncol 2010, doi: 10.1200/JCO.2009.27. 449.
18. Rischin D, Hicks RJ, Fisher R, et al. Prognostic significance of [18F]-misonidazole positron emission tomography-detected tumor hypoxia in patients with advanced head and neck cancer randomly assigned to chemoradiation with or without tirapazamine: a substudy of Trans-Tasman Radiation Oncology Group Study 98.02. J Clin Oncol 2006;24:2098-104.
19. Baker MA, Zeman EM, Hirst VK, Brown JM. Metabolism of SR 4233 by Chinese hamster ovary cells: basis of selective hypoxic cytotoxicity. Cancer Res 1988;48:5947-52.
20. Laderoute K, Wardman P, Rauth AM. Molecular mechanisms for the hypoxia-dependent activation of 3-amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233). Biochem Pharmacol 1988;37:1487-95.
21. Junnotula V, Sarkar U, Sinha S, Gates KS. Initiation of DNA strand cleavage by 1,2,4-benzotriazine 1,4-dioxide antitumor agents: mechanistic insight from studies of 3-methyl-1,2,4-benzotriazine 1,4-dioxide. J Am Chem Soc 2009;131:1015-24.
22. Shinde SS, Maroz A, Hay MP, Patterson AV, Denny WA, Anderson RF. Characterization of radicals formed following enzymatic reduction of 3-substituted analogues of the hypoxia-selective cytotoxin 3-amino-1,2,4- benzotriazine 1,4-dioxide (tirapazamine). J Am Chem Soc 2010;132:2591-9.
23. Siim BG, Pruijn FB, Sturman JR, et al. Selective potentiation of the hypoxic cytotoxicity of tirapazamine by its 1-N-oxide metabolite SR 4317. Cancer Res 2004;64:736-42.
24. Knox RJ, Chen S. Quinone reductase-mediated nitro-reduction: clinical applications. Methods Enzymol 2004;382:194-221. (Pubitemid 38240791)
25. Guise CP, Abbattista M, Singleton RS, et al. The bioreductive prodrug PR-104A is activated under aerobic conditions by human aldo-keto reductase 1C3. Cancer Res 2010;70:1573-84.
26. Koch CJ. Unusual oxygen concentration dependence of toxicity of SR-4233, a hypoxic cell toxin. Cancer Res 1993;53:3992-7.
27. 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.
28. 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.
29. 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.
30. Hicks KO, Myint H, Patterson AV, 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.
31. Wouters BG, Brown JM. Cells at intermediate oxygen levels can be more important than the "hypoxic fraction" in determining tumor response to fractionated radiotherapy. Radiat Res 1997;147:541-50.
32. Durand RE, Olive PL. Physiologic and cytotoxic effects of tirapazamine in tumor-bearing mice. Radiat Oncol Investig 1997;5:213-9.
33. Hicks KO, Fleming Y, Siim BG, Koch CJ, Wilson WR. Extravascular diffusion of tirapazamine: effect of metabolic consumption assessed using the multicellular layer model. Int J Radiat Oncol Biol Phys 1998;42:641-9.
34. Kyle AH, Minchinton AI. Measurement of delivery and metabolism of tirapazamine to tumour tissue using the multilayered cell culture model. Cancer Chemother Pharmacol 1999;43:213-20.
35. 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.
36. Hicks KO, Pruijn FB, Secomb TW, 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.
37. Pruijn FB, Sturman JR, Liyanage HDS, Hicks KO, Hay MP, Wilson WR. Extravascular transport of drugs in tumor tissue: effect of lipophilicity on diffusion of tirapazamine analogs in multicellular layer cultures. J Med Chem 2005;48:1079-87.
38. 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.
39. Hay MP, Gamage SA, Kovacs MS, et al. Structure-activity relationships of 1,2,4-benzotriazine 1,4-dioxides as hypoxia-selective analogues of tirapazamine. J Med Chem 2003;46:169-82.
40. Hay MP, Hicks KO, Pruijn FB, et al. Pharmacokinetic/pharmacodynamic model-guided identification of hypoxia-selective 1,2,4-benzotriazine 1,4-dioxides with antitumor activity: the role of extravascular transport. J Med Chem 2007;50:6392-404.
41. Hay MP, Pruijn FB, Gamage SA, et al. DNA-targeted 1,2,4-benzotriazine 1,4-dioxides: potent analogues of the hypoxiaselective cytotoxin tirapazamine. J Med Chem 2004;47:475-88.
42. Hay MP, Pchalek K, Pruijn FB, et al. Hypoxia-selective 3-alkyl 1,2,4-benzotriazine 1,4-dioxides: the influence of hydrogen bond donors on extravascular transport and antitumor activity. J Med Chem 2007;50:6654-64.
43. Hay MP, Hicks KO, Pchalek K, et al. Tricyclic [1,2,4]triazine 1,4-dioxides as hypoxia selective cytotoxins. J Med Chem 2008;51:6853-65.
44. 15N NMR assignment of tirapazamine and related 1,2,4-benzotriazine N-oxides. Magn Reson Chem 2006;44:948-54.
45. Pchalek K, Hay MP. Stille coupling reactions in the synthesis of hypoxia-selective 3-alkyl-1,2,4-benzotriazine 1,4-dioxide anticancer agents. J Org Chem 2006;71:6530-5.
46. Hicks KO, Pruijn FB, Baguley BC, Wilson WR. Extravascular transport of the DNA intercalator and topoisomerase poison N-[2-(dimethylamino)ethyl] acridine-4-carboxamide (DACA): diffusion and metabolism in multicellular layers of tumor cells. J Pharmacol Exp Ther 2001;297:1088-98.
47. Lee AE, Wilson WR. Hypoxia-dependent retinal toxicity of bioreductive anticancer prodrugs in mice. Toxicol Appl Pharmacol 2000;163:50-9.
48. Wang J, Ferry D, Hay MP, Patel R, Koch CJ, Wilson WR. Comparison of bioreductive metabolism of tirapazamine, its second generation analogue SN 30000 and hypoxia imaging agent EF5 in human tumor cell lines [Abstract]. In: Proc 101st Annual Meeting Am Assoc Cancer Res 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; 2010, abstract 2282.
49. Evans JW, Chernikova SB, Kachnic LA, et al. Homologous recombination is the principal pathway for the repair of DNA damage induced by tirapazamine in mammalian cells. Cancer Res 2008;68:257-65.
50. Senan S, Rampling R, Graham MA, et al. Phase I and pharmacokinetic study of tirapazamine (SR 4233) administered every three weeks. Clin Cancer Res 1997;3:31-8.