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Review

The therapeutic potential of O6-alkylguanine DNA alkyltransferase inhibitors

, MD BSc (Hons) MBBS MRCP (UK) & , MD BA BM BCh MRCP (UK) PhD
Pages 1573-1584 | Published online: 09 Oct 2007

Bibliography

  • PEGG AE, DOLAN ME, MOSCHEL RC: Structure, function, and inhibition of O6-alkylguanine-DNA alkyltransferase. Prog. Nucleic Acid Res. Mol. Biol. (1995) 51:167-223.
  • GONZAGA PE, BRENT TP: Affinity purification and characterization of human O6-alkylguanine-DNA alkyltransferase complexed with BCNU-treated, synthetic oligonucleotide. Nucleic Acids Res. (1989) 17:6581-6590.
  • ESTELLER M, HERMAN JG: Generating mutations but providing chemosensitivity: the role of O6-methylguanine DNA methyltransferase in human cancer. Oncogene (2004) 23:1-8.
  • PEGG AE: Mammalian O6-alkylguanine-DNA alkyltransferase: regulation and importance in response to alkylating carcinogenic and therapeutic agents. Cancer Res. (1990) 50:6119-6129.
  • MACDONALD DR: Temozolomide for recurrent high-grade glioma. Semin. Oncol. (2001) 28:3-12.
  • LENS MB, EISEN TG: Systemic chemotherapy in the treatment of malignant melanoma. Expert Opin. Pharmacother. (2003) 4(12):2205-2211.
  • DRABLOS F, FEYZI E, AAS PA et al.: Alkylation damage in DNA and RNA – repair mechanisms and medical significance. DNA Repair (Amst.) (2004) 3:1389-1407.
  • MIDDLETON MR, MARGISON GP: Improvement of chemotherapy efficacy by inactivation of a DNA-repair pathway. Lancet Oncol. (2003) 4:37-44.
  • SABHARWAL A, MIDDLETON MR: Exploiting the role of O6-methylguanine-DNA-methyltransferase (MGMT) in cancer therapy. Curr. Opin. Pharmacol. (2006) 6:355-363.
  • TONG WP, KIRK MC, LUDLUM DB: Formation of the cross-link 1-[N3-deoxycytidyl),2-[N1-deoxyguanosinyl]ethane in DNA treated with N,N′-bis(2-chloroethyl)-N-nitrosourea. Cancer Res. (1982) 42:3102-3105.
  • GERSON SL: Clinical relevance of MGMT in the treatment of cancer. J. Clin. Oncol. (2002) 20:2388-2399.
  • PAULY GT, HUGHES SH, MOSCHEL RC: Response of repair-competent and repair-deficient Escherichia coli to three O6-substituted guanines and involvement of methyl-directed mismatch repair in the processing of O6-methylguanine residues. Biochemistry (1994) 33:9169-9177.
  • SOULIOTIS VL, BOUSSIOTIS VA, PANGALIS GA, KYRTOPOULOS SA: In vivo formation and repair of O6-methylguanine in human leukocyte DNA after intravenous exposure to dacarbazine. Carcinogenesis (1991) 12:285-288.
  • STOJIC L, BRUN R, JIRICNY J: Mismatch repair and DNA damage signalling. DNA Repair (Amst.) (2004) 3:1091-1101.
  • ARMSTRONG MJ, GALLOWAY SM: Mismatch repair provokes chromosome aberrations in hamster cells treated with methylating agents or 6-thioguanine, but not with ethylating agents. Mutat. Res. (1997) 373:167-178.
  • KAINA B: Mechanisms and consequences of methylating agent-induced SCEs and chromosomal aberrations: a long road traveled and still a far way to go. Cytogenet. Genome Res. (2004) 104:77-86.
  • AYI TC, LOH KC, ALI RB, LI BF: Intracellular localization of human DNA repair enzyme methylguanine-DNA methyltransferase by antibodies and its importance. Cancer Res. (1992) 52:6423-6430.
  • GERSON SL, PHILLIPS W, KASTAN M, DUMENCO LL, DONOVAN C: Human CD34+ hematopoietic progenitors have low, cytokine-unresponsive O6-alkylguanine-DNA alkyltransferase and are sensitive to O6-benzylguanine plus BCNU. Blood (1996) 88:1649-1655.
  • KOKKINAKIS DM, AHMED MM, DELGADO R et al.: Role of O6-methylguanine-DNA methyltransferase in the resistance of pancreatic tumors to DNA alkylating agents. Cancer Res. (1997) 57:5360-5368.
  • MARGISON GP, POVEY AC, KAINA B, SANTIBANEZ KOREF MF: Variability and regulation of O6-alkylguanine-DNA alkyltransferase. Carcinogenesis (2003) 24:625-635.
  • SPIRO TP, GERSON SL, LIU L et al.: O6-benzylguanine: a clinical trial establishing the biochemical modulatory dose in tumor tissue for alkyltransferase-directed DNA repair. Cancer Res. (1999) 59:2402-2410.
  • BRENT TP, VON WM, PEGRAM CN, BIGNER DD: Immunoaffinity purification of human O6-alkylguanine-DNA alkyltransferase using newly developed monoclonal antibodies. Cancer Res. (1990) 50:58-61.
  • HARRIS LC, POTTER PM, TANO K et al.: Characterization of the promoter region of the human O6-methylguanine-DNA methyltransferase gene. Nucleic Acids Res. (1991) 19:6163-6167.
  • BAE SI, LEE HS, KIM SH, KIM WH: Inactivation of O6-methylguanine-DNA methyltransferase by promoter CpG island hypermethylation in gastric cancers. Br. J. Cancer (2002) 86:1888-1892.
  • VON WRONSKI MA, BRENT TP: Effect of 5-azacytidine on expression of the human DNA repair enzyme O6-methylguanine-DNA methyltransferase. Carcinogenesis (1994) 15:577-582.
  • SCUDIERO DA, MEYER SA, CLATTERBUCK BE et al.: Sensitivity of human cell strains having different abilities to repair O6-methylguanine in DNA to inactivation by alkylating agents including chloroethylnitrosoureas. Cancer Res. (1984) 44:2467-2474.
  • GERSON SL, ZBOROWSKA E, NORTON K, GORDON NH, WILLSON JK: Synergistic efficacy of O6-benzylguanine and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) in a human colon cancer xenograft completely resistant to BCNU alone. Biochem. Pharmacol. (1993) 45:483-491.
  • ISHIZAKI K, TSUJIMURA T, YAWATA H et al.: Transfer of the E. coli O6-methylguanine methyltransferase gene into repair-deficient human cells and restoration of cellular resistance to N-methyl-N′-nitro-N-nitrosoguanidine. Mutat. Res. (1986) 166:135-141.
  • CHEN JM, ZHANG YP, WANG C et al.: O6-Methylguanine-DNA methyltransferase activity in human tumors. Carcinogenesis (1992) 13:1503-1507.
  • BELANICH M, PASTOR M, RANDALL T et al.: Retrospective study of the correlation between the DNA repair protein alkyltransferase and survival of brain tumor patients treated with carmustine. Cancer Res. (1996) 56:783-788.
  • JAECKLE KA, EYRE HJ, TOWNSEND JJ et al.: Correlation of tumor O6 methylguanine-DNA methyltransferase levels with survival of malignant astrocytoma patients treated with bis-chloroethylnitrosourea: a Southwest Oncology Group study. J. Clin. Oncol. (1998) 16:3310-3315.
  • FRIEDMAN HS, MCLENDON RE, KERBY T et al.: DNA mismatch repair and O6-alkylguanine-DNA alkyltransferase analysis and response to Temodal in newly diagnosed malignant glioma. J. Clin. Oncol. (1998) 16:3851-3857.
  • ESTELLER M, GARCIA-FONCILLAS J, ANDION E et al.: Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N. Engl. J. Med. (2000) 343:1350-1354.
  • HEGI ME, DISERENS AC, GODARD S et al.: Clinical trial substantiates the predictive value of O6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide. Clin. Cancer Res. (2004) 10:1871-1874.
  • HEGI ME, DISERENS AC, GORLIA T et al.: MGMT gene silencing and benefit from temozolomide in glioblastoma. N. Engl. J. Med. (2005) 352:997-1003.
  • MA S, EGYHAZI S, RINGBORG U, HANSSON J: Immunohistochemical analysis of DNA mismatch repair protein and O6-methylguanine-DNA methyltransferase in melanoma metastases in relation to clinical response to DTIC-based chemotherapy. Oncol. Rep. (2002) 9:1015-1019.
  • MIDDLETON MR, LUNN JM, MORRIS C et al.: O6-Methylguanine-DNA methyltransferase in pretreatment tumour biopsies as a predictor of response to temozolomide in melanoma. Br. J. Cancer (1998) 78:1199-1202.
  • PANELLA TJ, SMITH DC, SCHOLD SC et al.: Modulation of O6-alkylguanine-DNA alkyltransferase-mediated carmustine resistance using streptozotocin: a Phase I trial. Cancer Res. (1992) 52:2456-2459.
  • MICETICH KC, FUTSCHER B, KOCH D, FISHER RI, ERICKSON LC: Phase I study of streptozocin- and carmustine-sequenced administration in patients with advanced cancer. J. Natl. Cancer Inst. (1992) 84:256-260.
  • SMITH DC, GERSON SL, LIU L et al.: Carmustine and streptozocin in refractory melanoma: an attempt at modulation of O-alkylguanine-DNA-alkyltransferase. Clin. Cancer Res. (1996) 2:1129-1134.
  • LEE SM, MARGISON GP, WOODCOCK AA, THATCHER N: Sequential administration of varying doses of dacarbazine and fotemustine in advanced malignant melanoma. Br. J. Cancer (1993) 67:1356-1360.
  • GANDER M, LEYVRAZ S, DECOSTERD L et al.: Sequential administration of temozolomide and fotemustine: depletion of O6-alkyl guanine-DNA transferase in blood lymphocytes and in tumours. Ann. Oncol. (1999) 10:831-838.
  • LEE SM, THATCHER N, CROWTHER D, MARGISON GP: Inactivation of O6-alkylguanine-DNA alkyltransferase in human peripheral blood mononuclear cells by temozolomide. Br. J. Cancer (1994) 69:452-456.
  • MIDDLETON MR, LEE SM, ARANCE A et al.: O6-methylguanine formation, repair protein depletion and clinical outcome with a 4 h schedule of temozolomide in the treatment of advanced melanoma: results of a Phase II study. Int. J. Cancer (2000) 88:469-473.
  • BROCK CS, NEWLANDS ES, WEDGE SR et al.: Phase I trial of temozolomide using an extended continuous oral schedule. Cancer Res. (1998) 58:4363-4367.
  • PEGG AE, BOOSALIS M, SAMSON L et al.: Mechanism of inactivation of human O6-alkylguanine-DNA alkyltransferase by O6-benzylguanine. Biochemistry (1993) 32:11998-12006.
  • PEGG AE: Repair of O(6)-alkylguanine by alkyltransferases. Mutat. Res. (2000) 462:83-100.
  • MAGULL-SELTENREICH A, ZELLER WJ: Sensitization of human colon tumour cell lines to carmustine by depletion of O6-alkylguanine-DNA alkyltransferase. J. Cancer Res. Clin. Oncol. (1995) 121:225-229.
  • FRIEDMAN HS, KOKKINAKIS DM, PLUDA J et al.: Phase I trial of O6-benzylguanine for patients undergoing surgery for malignant glioma. J. Clin. Oncol. (1998) 16:3570-3575.
  • FRIEDMAN HS, PLUDA J, QUINN JA et al.: Phase I trial of carmustine plus O6-benzylguanine for patients with recurrent or progressive malignant glioma. J. Clin. Oncol. (2000) 18:3522-3528.
  • QUINN JA, DESJARDINS A, WEINGART J et al.: Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma. J. Clin. Oncol. (2005) 23:7178-7187.
  • QUINN JA, PLUDA J, DOLAN ME et al.: Phase II trial of carmustine plus O(6)-benzylguanine for patients with nitrosourea-resistant recurrent or progressive malignant glioma. J. Clin. Oncol. (2002) 20:2277-2283.
  • GAJEWSKI TF, SOSMAN J, GERSON SL et al.: Phase II trial of the O6-alkylguanine DNA alkyltransferase inhibitor O6-benzylguanine and 1,3-bis(2-chloroethyl)-1-nitrosourea in advanced melanoma. Clin. Cancer Res. (2005) 11:7861-7865.
  • RYAN CW, DOLAN ME, BROCKSTEIN BB et al.: A Phase II trial of O6-benzylguanine and carmustine in patients with advanced soft tissue sarcoma. Cancer Chemother. Pharmacol. (2006) 58:634-639.
  • BATTS ED, MAISEL C, KANE D et al.: O(6)-benzylguanine and BCNU in multiple myeloma: a Phase II trial. Cancer Chemother. Pharmacol. (2007) 60:415-421.
  • MCELHINNEY RS, DONNELLY DJ, MCCORMICK JE et al.: Inactivation of O6-alkylguanine-DNA alkyltransferase. 1. Novel O6-(hetarylmethyl)guanines having basic rings in the side chain. J. Med. Chem. (1998) 41:5265-5271.
  • MIDDLETON MR, KELLY J, THATCHER N et al.: O(6)-(4-bromothenyl)guanine improves the therapeutic index of temozolomide against A375M melanoma xenografts. Int. J. Cancer (2000) 85:248-252.
  • MIDDLETON MR, THATCHER N, MCMURRY TB et al.: Effect of O6-(4-bromothenyl)guanine on different temozolomide schedules in a human melanoma xenograft model. Int. J. Cancer (2002) 100:615-617.
  • RANSON M, MIDDLETON MR, BRIDGEWATER J et al.: Lomeguatrib, a potent inhibitor of O6-alkylguanine-DNA-alkyltransferase: Phase I safety, pharmacodynamic, and pharmacokinetic trial and evaluation in combination with temozolomide in patients with advanced solid tumors. Clin. Cancer Res. (2006) 12:1577-1584.
  • RANSON M, HERSEY P, THOMPSON D et al.: Randomized trial of the combination of lomeguatrib and temozolomide compared with temozolomide alone in chemotherapy naive patients with metastatic cutaneous melanoma. J. Clin. Oncol. (2007) 25:2540-2545.
  • CAPORASO P, TURRIZIANI M, VENDITTI A et al.: Novel role of triazenes in haematological malignancies: pilot study of temozolomide, lomeguatrib and IL-2 in the chemo-immunotherapy of acute leukaemia. DNA Repair (Amst.) (2007) 6(8):1179-1186.
  • WANG CC, LI J, TEO CS, LEE T: The delivery of BCNU to brain tumors. J. Control. Rel. (1999) 61:21-41.
  • WEINGART J, GROSSMAN SA, CARSON KA et al.: Phase I trial of polifeprosan 20 with carmustine implant plus continuous infusion of intravenous O6-benzylguanine in adults with recurrent malignant glioma: new approaches to brain tumor therapy CNS consortium trial. J. Clin. Oncol. (2007) 25:399-404.
  • QUINN JA, VREDENBURGH JJ, RICH JN et al.: Phase II trial of gliadel plus O6-benzylguanine (O6-BG) for patients with recurrent glioblastoma multiforme. Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings (2006) 24(S18 Suppl. 20):1568.
  • REINHARD J, HULL WE, VON DER LIETH CW et al.: Monosaccharide-linked inhibitors of O(6)-methylguanine-DNA methyltransferase (MGMT): synthesis, molecular modeling, and structure–activity relationships. J. Med. Chem. (2001) 44:4050-4061.
  • REESE JS, KOC ON, LEE KM et al.: Retroviral transduction of a mutant methylguanine DNA methyltransferase gene into human CD34 cells confers resistance to O6-benzylguanine plus 1,3-bis(2-chloroethyl)-1-nitrosourea. Proc. Natl. Acad. Sci. USA (1996) 93:14088-14093.
  • SAWAI N, ZHOU S, VANIN EF et al.: Protection and in vivo selection of hematopoietic stem cells using temozolomide, O6-benzylguanine, and an alkyltransferase-expressing retroviral vector. Mol. Ther. (2001) 3:78-87.
  • TROBRIDGE G, BEARD BC, KIEM HP: Hematopoietic stem cell transduction and amplification in large animal models. Hum. Gene Ther. (2005) 16:1355-1366.
  • SORG UR, KLEFF V, FANAEI S et al.: O(6)-methylguanine-DNA-methyltransferase (MGMT) gene therapy targeting haematopoietic stem cells: studies addressing safety issues. DNA Repair (Amst.) (2007) 6(8):1197-1209.
  • FRIEDMAN HS, PEGG AE, JOHNSON SP et al.: Modulation of cyclophosphamide activity by O6-alkylguanine-DNA alkyltransferase. Cancer Chemother. Pharmacol. (1999) 43:80-85.
  • FRIEDMAN HS, KEIR S, PEGG AE et al.: O6-benzylguanine-mediated enhancement of chemotherapy. Mol. Cancer Ther. (2002) 1:943-948.
  • KLASA RJ, GILLUM AM, KLEM RE, FRANKEL SR: Oblimersen Bcl-2 antisense: facilitating apoptosis in anticancer treatment. Antisense Nucleic Acid Drug Dev. (2002) 12:193-213.
  • BARVAUX VA, LORIGAN P, RANSON M et al.: Sensitization of a human ovarian cancer cell line to temozolomide by simultaneous attenuation of the Bcl-2 antiapoptotic protein and DNA repair by O6-alkylguanine-DNA alkyltransferase. Mol. Cancer Ther. (2004) 3:1215-1220.
  • JIRICNY J: The multifaceted mismatch-repair system. Nat. Rev. Mol. Cell Biol. (2006) 7:335-346.
  • BIGNAMI M, O'DRISCOLL M, AQUILINA G, KARRAN P: Unmasking a killer: DNA O(6)-methylguanine and the cytotoxicity of methylating agents. Mutat. Res. (2000) 462:71-82.
  • KAINA B, OCHS K, GROSCH S et al.: BER, MGMT, and MMR in defense against alkylation-induced genotoxicity and apoptosis. Prog. Nucleic Acid Res. Mol. Biol. (2001) 68:41-54.
  • MADHUSUDAN S, MIDDLETON MR: The emerging role of DNA repair proteins as predictive, prognostic and therapeutic targets in cancer. Cancer Treat. Rev. (2005) 31:603-617.
  • CALABRESE CR, BATEY MA, THOMAS HD et al.: Identification of potent nontoxic poly (ADP-ribose) polymerase-1 inhibitors: chemopotentiation and pharmacological studies. Clin. Cancer Res. (2003) 9:2711-2718.
  • CURTIN NJ, WANG LZ, YIAKOUVAKI A et al.: Novel poly (ADP-ribose) polymerase-1 inhibitor, AG14361, restores sensitivity to temozolomide in mismatch repair-deficient cells. Clin. Cancer Res. (2004) 10:881-889.
  • CHENG CL, JOHNSON SP, KEIR ST et al.: Poly (ADP-ribose) polymerase-1 inhibition reverses temozolomide resistance in a DNA mismatch repair-deficient malignant glioma xenograft. Mol. Cancer Ther. (2005) 4:1364-1368.
  • TENTORI L, LEONETTI C, SCARSELLA M et al.: Poly (ADP-ribose) glycohydrolase inhibitor as chemosensitiser of malignant melanoma for temozolomide. Eur. J. Cancer (2005) 41:2948-2957.
  • MIKNYOCZKI SJ, JONES-BOLIN S, PRITCHARD S et al.: Chemopotentiation of temozolomide, irinotecan, and cisplatin activity by CEP-6800, a poly (ADP-ribose) polymerase inhibitor. Mol. Cancer Ther. (2003) 2:371-382.
  • ROUNTREE MR, BACHMAN KE, HERMAN JG, BAYLIN SB: DNA methylation, chromatin inheritance, and cancer. Oncogene (2001) 20:3156-3165.
  • KLUMP B, HSIEH CJ, HOLZMANN K, GREGOR M, PORSCHEN R: Hypermethylation of the CDKN2/p16 promoter during neoplastic progression in Barrett's esophagus. Gastroenterology (1998) 115:1381-1386.
  • EADS CA, LORD RV, KURUMBOOR SK et al.: Fields of aberrant CpG island hypermethylation in Barrett's esophagus and associated adenocarcinoma. Cancer Res. (2000) 60:5021-5026.
  • BIAN YS, OSTERHELD MC, FONTOLLIET C, BOSMAN FT, BENHATTAR J: p16 inactivation by methylation of the CDKN2A promoter occurs early during neoplastic progression in Barrett's esophagus. Gastroenterology (2002) 122:1113-1121.

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