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Review

Therapeutic potential of drugs to modulate DNA repair in cancer

Pages 783-799 | Published online: 15 May 2007

Bibliography

  • HUTCHINSON F: Chemical changes induced in DNA by ionising radiation. In: Progress in Nucleic Acid Research and Molecular Biology (1985) 32:115-154.
  • HOEIJMAKERS JH: Genome maintenance mechanisms for preventing cancer. Nature (2001) 411:366-374.
  • BARTKOVA J, HOREJSI Z, KOED K et al.: DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature (2005) 434:864-870.
  • JACKSON AL AND LOEB LA: The contribution of endogenous sources of DNA damage to the multiple mutations in cancer. Mutat. Res. (2001) 477:7-21.
  • VENKITARAMAN AR: Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell (2002) 108:171-182.
  • BRONNER CE, BAKER SM, MORRISON PT et al.: Mutation in the DNA mismatch repair gene homologue hMLH1 is associated with hereditary non-polyposis colon cancer. Nature (1994) 368:258-261
  • KAINA B, ZIOUTA A, OCHS K, COQUERELLE T: Chromosomal instability, reproductive cell death and apoptosis induced by O6-methylguanine in Mex-, Mex+ and methylation-tolerant mismatch repair compromised cells: facts and models. Mutat. Res. (1997) 381:227-241.
  • TUTT A, BERTWISTLE D, VALENTINE J et al.: Mutation in Brca2 stimulates error-prone homology-directed repair of DNA double-strand breaks occurring between repeated sequences. EMBO J. (2001) 20:4704-4716.
  • SABHARWAL A, MIDDLETON MR: Exploiting the role of O6-methylguanine-DNA-methyltransferase (MGMT) in cancer therapy. Curr. Opin. Pharmacol. (2006) 6:355-363.
  • PEGG AE: Mammalian O6-alkylguanine-DNA alkyltransferase: regulation and importance in response to alkylating carcinogenic and therapeutic agents. Cancer Res. (1990) 50:6119-6129.
  • 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.
  • CHEN JM, ZHANG YP, WANG C, SUN Y, FUJIMOTO J, IKENAGA M: O6-methylguanine-DNA methyltransferase activity in human tumors. Carcinogenesis (1992) 13:1503-1507.
  • WANI G, D’AMBROSIO SM: Expression of the O6-alkylguanine-DNA alkyltransferase gene is elevated in human breast tumor cells. Anti-Cancer Res. (1997) 17:4311-4315.
  • SCHOLD SC Jr, BRENT TP, VON HOFEL E et al.: O6-alkylguanine-DNA alkyltransferase and sensitivity to procarbazine in human brain-tumor xenografts. J. Neurosurg. (1989) 70:573-577.
  • YAROSH DB: The role of O6-methylguanine-DNA methyltransferase in cell survival, mutagenesis and carcinogenesis. Mutat. Res. (1985) 145:1-16.
  • 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.
  • 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.
  • DOLAN ME, MORIMOTO K, PEGG AE: Reduction of O6-alkylguanine- DNA alkyltransferase activity in HeLa cells treated with O6-akylguanines. Cancer Res. (1985) 45(12 Pt. 1):6413-6417.
  • YAROSH DB, HURST-CALDERONE S, BABICH MA, DAY RS III: Inactivation of O6-methylguanine-DNA methyltransferase and sensitization of human tumor cells to killing by chloroethylnitrosourea by O6-methylguanine as a free base. Cancer Res. (1986) 46(4 Pt. 1):1663-1668.
  • DOLAN ME, LARKIN Gl, ENGLISH HF, PEGG AE: Depletion of O6-alkylguanine-DNA alkyltransferase activity in mammalian tissues and human tumor xenografts in nude mice by treatment with O6- methylguanine. Cancer Chemother. Pharmacol. (1989) 25(2):103-108.
  • DOLAN ME, MOSCHEL RC, PEGG AE Depletion of mammalian O6-alkylguanine-DNA alkyltransferase activity by O6-benzylguanine provides a means to evaluate the role of this protein in protection against carcinogenic and therapeutic alkylating agents. Proc. Natl. Acad. Sci. USA (1990) 87:5368-5372.
  • WEDGE SR, PORTEUS JK, MAY BL, NEWLANDS ES: Potentiation of temozolomide and BCNU cytotoxicity by O6-benzylguanine: a comparative study in vitro. Br. J. Cancer (1996) 73:482-490.
  • RABIK CA, NJOKU MC, DOLAN ME: Inactivation of O6-alkylguanine DNA alkyltransferase as a means to enhance chemotherapy. Cancer Treat. Rev. (2006) 32:261-276.
  • MCELHINNEY RS, MCMURRY TB, MARGISON GP: O6-alkylguanine-DNA alkyltransferase inactivation in cancer chemotherapy. Mini-Rev. Med. Chem. (2003) 3:471-485.
  • MIDDLETON MR, KELLY J, THATCHER N et al.: O6-(4-bromothenyl)guanine improves the therapeutic index of temozolomide against A375M melanoma xenografts. Int. J. Cancer (2000) 85:248-252.
  • 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.
  • GERSON SL: MGMT: its role in cancer aetiology and cancer therapeutics. Nat. Rev. Cancer (2004) 4:296-307.
  • 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.
  • ROITT IM: The inhibition of carbohydrate metabolism in ascites-tumour cells by ethyleneimines. Biochem. J. (1956) 63:300-307.
  • CHAMBON P, WEILL JD, MANDEL P: Nicotinamide mononucleotide activation of new DNA-dependent polyadenylic acid synthesizing nuclear enzyme. Biochem. Biophys. Res. Commun. (1963) 11:39-43.
  • DE MURCIA G, MENISSIER DE MURCIA J: Poly(ADP-ribose) polymerase: a molecular nick-sensor. Trends Biochem. Sci. (1994) 19:172-176.
  • SCHREIBER V, DANTZER F, AME JC, DE MURCIA G: Poly(ADP-ribose): novel functions for an old molecule. Nat. Rev. Mol. Cell Biol. (2006) 7:517-528.
  • SCHREIBER V, AME J-C, DOLLE P et al.: Poly(ADP-ribose) polymerase-2 (PARP-2) is required for efficient base excision repair in association with PARP-1 and XRCC1. J. Biol. Chem. (2002) 277:23028-23036.
  • MENDOZA-ALVAREZ H, ALVAREZ-GONZALEZ R: Poly(ADP-ribose) polymerase is a catalytic dimer and the automodification reaction is intermolecular. J. Biol. Chem. (1993) 268:22575-22580.
  • POIRIER GG, DE MURCIA G, JONGSTRA-BILEN J, NIEDERGANG C, MANDEL P: Poly(ADP-ribosyl)ation of polynucleosomes causes relaxation of chromatin structure. Proc. Natl. Acad. Sci. USA (1982) 79:3423-3427.
  • REALINI CA, ALTHAUS FR: Histone shuttling by poly(ADP-ribosylation). J. Biol. Chem. (1992) 267:18858-18865.
  • EL-KHAMISY SF, MASUTANI M, SUZUKI H, CALDECOTT KW: A requirement for PARP-1 for the assembly or stability of XRCC1 nuclear foci at sites of oxidative DNA damage. Nucleic Acids Res. (2003) 31:5526-5533.
  • MASSON M, NIEDERGANG C, SCHREIBER V, MULLER S, MENISSIER-DE MURCIA J, DE MURCIA G: XRCC1 is specifically associated with poly(ADP-ribose) polymerase and negatively regulates its activity following DNA damage. Mol. Cell. Biol. (1998) 18:3563-3571.
  • CALDECOTT KW: XRCC1 and DNA strand break repair. DNA Repair (Amst.) (2003) 2:955-969.
  • DANTZER F, DE LA RUBIA G, MENISSIER-DE MURCIA J, HOSTOMSKY Z, DE MURCIA G, SCHREIBER V: Base excision repair is impaired in mammalian cells lacking Poly(ADP-ribose) polymerase-1. Biochemistry (2000) 39:7559-7569.
  • DANTZER F, SCHREIBER V, NIEDERGANG C et al.: Involvement of poly(ADP-ribose) polymerase in base excision repair. Biochimie (1999) 81:69-75.
  • BENJAMIN R C, GILL D M: Poly(ADP-ribose) synthesis in vitro programmed by damaged DNA: comparison of DNA molecules containing different types of strand breaks. J. Biol. Chem. (1980) 255:10502-10508.
  • RUSCETTI T, LEHNERT BE, HALBROOK J et al.: Stimulation of the DNA-dependent protein kinase by poly(ADP-ribose) polymerase. J. Biol. Chem. (1998) 273:14461-14467.
  • AUDEBERT M, SALLES B, WEINFELD M, CALSOU P: Involvement of polynucleotide kinase in a poly(ADP-ribose) polymerase-1-dependent DNA double strand breaks rejoining pathway. J. Mol. Biol. (2006) 356:257-265.
  • WANG M, WU W, WU W et al.: PARP-1 and Ku compete for repair of DNA double strand breaks by distinctive NHEJ pathway. Nucl. Acids Res. (2006) 34:6170-6182.
  • BOULTON S, KYLE S, DURKACZ BW: Interactive effects of poly(ADP-ribose) polymerase and DNA-dependent protein kinase on cellular responses to DNA damage. Carcinogenesis (Lond.) (1999) 20:199-203
  • VEUGER SJ, CURTIN NJ, RICHARDSON CJ, SMITH GC, DURKACZ BW: Radiosensitization and DNA repair inhibition by the combined use of novel inhibitors of DNA-dependent protein kinase and poly(ADP-ribose) polymerase-1. Cancer Res. (2003) 63:6008-6015.
  • VEUGER SJ, CURTIN NJ, SMITH GC, DURKACZ BW: Effects of novel inhibitors of poly(ADP-ribose) polymerase-1 and the DNA-dependent protein kinase on enzyme activities and DNA repair. Oncogene (2004) 23:7322-7329.
  • PURNELL MR, WHISH WJ: Novel inhibitors of poly(ADP-ribose) synthetase. Biochem. J. (1980) 185:775-777.
  • DURKACZ BW, OMIDIJI O, GRAY DA, SHALL S: (ADP-ribose)n participates in DNA excision repair. Nature (1980) 283:593-596.
  • GRIFFIN RJ, PEMBERTON LC, RHODES D et al.: Novel potent inhibitors of the DNA repair enzyme poly(ADP-ribose)polymerase (PARP). Anti-Cancer Drug Des. (1995) 10:507-514.
  • SUTO MJ, TURNER WR, ARUNDEL-SUTO CM, WERBEL LM, SEBOLT-LEOPOLD JS: Dihydroisoquinolinones: the design and synthesis of a new series of potent inhibitors of poly(ADP-ribose) polymerase. Anti-Cancer Drug Des. (1991) 6:107-117.
  • BOWMAN KJ, NEWELL DR, CALVERT AH, CURTIN NJ: Differential effects of the poly (ADP-ribose) polymerase (PARP) inhibitor NU1025 on topoisomerase I and II inhibitor cytotoxicity in L1210 cells in vitro. Br. J. Cancer (2001) 84:106-112.
  • BANASIK M, KOMURA H, SHIMOYAMA M, UEDA K: Specific inhibitors of poly(ADP-ribose) synthetase and mono(ADP-ribosyl)transferase. J. Biol. Chem. (1992) 267:1569-1575.
  • DELANEY CA, WANG LZ, KYLE S et al.: Potentiation of temozolomide and topotecan growth inhibition and cytotoxicity by novel poly(adenosine diphosphoribose) polymerase inhibitors in a panel of human tumor cell lines. Clin. Cancer Res. (2000) 6:2860-2867.
  • CURTIN NJ: PARP inhibitors for cancer therapy. Expert Rev. Mol. Med. (2005) 7:1-20.
  • JAGTAP P, SZABO C: Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors. Nat. Rev. Drug Discov. (2005) 4:421-440.
  • TENTORI L, GRAZIANI G: Chemopotentiation by PARP inhibitors in cancer therapy. Pharmacol. Res. (2005) 52:25-33.
  • WOON EC, THREADGILL MD: Poly(ADP-ribose)polymerase inhibition – where now? Curr. Med. Chem. (2005) 12:2373-2392.
  • TENTORI L, PORTARENA I, GRAZIANI G: Potential clinical applications of poly(ADP-ribose) polymerase (PARP) inhibitors. Pharmacol. Res. (2002) 45:73-78.
  • BOULTON S, PEMBERTON LC, PORTEOUS JK et al.: Potentiation of temozolomide-induced cytotoxicity: a comparative study of the biological effects of poly(ADP-ribose) polymerase inhibitors. Br. J. Cancer (1995) 72:849-856.
  • TENTORI L, LEONETTI C, SCARSELLA M et al.: Systemic administration of GPI 15427: a novel poly(ADP-ribose) polymerase-1 inhibitor, increases the antitumor activity of temozolomide against intracranial melanoma, glioma, lymphoma. Clin. Cancer Res. (2003) 9:5370-5379.
  • LOH VM JR, COCKROFT X-L, DILLON KJ et al.: Phthalazinones. Part 1: The design and synthesis of a novel series of potent inhibitors of poly(ADP-ribose)polymerase. Bio-org. Med. Chem. Lett. (2005) 15:2235-2238.
  • COCKROFT X-L, DILLON KJ, DIXON L et al.: Phthalazinones 2: optimisation and synthesis of novel inhibitors of poly(ADP-ribose) polymerase. Bio-org. Med. Chem. Lett. (2006) 16:1040-1044.
  • 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.
  • CALABRESE CR, ALMASSY R, BARTON S et al.: Anticancer chemosensitization and radiosensitization by the novel poly(ADP-ribose) polymerase-1 inhibitor AG14361. J. Natl. Cancer Inst. (2004) 96:56-67.
  • 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.
  • 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.
  • HERMAN JG, UMAR A, POLYAK K et al.: Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma. Proc. Natl. Acad. Sci. USA (1998) 95:6870-6875.
  • LIU L, TAVERNA P, WHITACRE CM et al.: Pharmacological disruption of base excision repair sensitizes mismatch repair-deficient and –proficient colon cancer cells to methylating agents. Clin. Cancer Res. (1999) 5:2908-2917.
  • CURTIN NJ, WANG, L-Z, YIAKOUVAKI A et al.: Novel PARP-1 inhibitor, AG14361:restores sensitivity to temozolomide in mismatch repair deficient cells. Clin. Cancer Res. (2004) 10:881-889.
  • TENTORI L, LEONETTI C, SCARSELLA M et al.: Inhibition of poly(ADP-ribose) polymerase prevents irinotecan-induced intestinal damage and enhances irinotecan/temozolomide efficacy against colon carcinoma. FASEB J. (2006) 20:1709-1711.
  • 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.
  • YUNG TM, SATO S, SATOH MS: Poly(ADP-ribosyl)ation as a DNA damage-induced post-translational modification regulating poly(ADP-ribose) polymerase-1-topoisomerase I interaction. J. Biol. Chem. (2004) 279:39686-39696.
  • SMITH LM, WILLMORE E, AUSTIN CA, CURTIN NJ: The novel poly(ADP-Ribose) polymerase inhibitor, AG14361:sensitizes cells to topoisomerase I poisons by increasing the persistence of DNA strand breaks. Clin. Cancer Res. (2005) 11:8449-8457.
  • PLO I, LIAO ZY, BARCELO JM et al.: Association of XRCC1 and tyrosyl DNA phosphodiesterase (Tdp1) for the repair of topoisomerase I-mediated DNA lesions. DNA Repair (Amst.) (2003) 2:1087-1100.
  • MALANGA M, ALTHAUS FR: Poly(ADP-ribose) reactivates stalled DNA topoisomerase I and Induces DNA strand break resealing. J. Biol. Chem. (2004) 279:5244-5248.
  • BEN-HUR E: Involvement of poly(ADP-ribose) in the radiation response of mammalian cells. Int. J. Radiat. Biol. (1984) 46:659-671.
  • ARUNDEL-SUTO CM, SCAVONE SV, TURNER WR et al.: Effects of PD128763:a new potent inhibitor of poly(ADP-ribose) polymerase, on X-ray induced cellular recovery processes in Chinese hamster V79 cells. Radiat. Res. (1991) 126:367-371.
  • BOWMAN K J, WHITE A, GOLDING BT et al.: Potentiation of anticancer agent cytotoxicity by the potent poly(ADP-ribose) polymerase inhibitors, NU1025 and NU1064. Br. J. Cancer (1998) 78:1269-1277.
  • VOGELSTEIN B, KINZLER KW: Cancer genes and the pathways they control. Nat. Med. (2004) 10:789-799.
  • OIKAWA A, TOHDA H, KANAI M, MIWA M, SUGIMURA T: Inhibitors of poly(adenosine diphosphate ribose) polymerase induce sister chromatid exchanges. Biochem. Biophys. Res. Commun. (1980) 97:1311-1316.
  • LINDAHL T, SATOH MS, POIRIER GG, KLUNGLAND A: Post-translational modification of poly(ADP-ribose) polymerase induced by DNA strand breaks. Trends Biochem. Sci. (1995) 20:405-411.
  • SCHULTZ N, LOPEZ E, SALEH-GOHARI N, HELLEDAY T: Poly(ADP-ribose) polymerase (PARP-1) has a controlling role in homologous recombination. Nucleic Acids Res. (2003) 31:4959-4964.
  • BRYANT HE, SCHULTZ N, THOMAS HD et al.: Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose)polymerase. Nature (2005) 434:913-917.
  • FARMER H, MCCABE N, LORD CJ et al.: Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature (2005) 434:917-921.
  • HARTWELL L P SZANKASI C ROBERTS A MURRAY, FRIEND S: Integrating genetic approaches into the discovery of anticancer drugs. Science (1997) 278:1064-1068.
  • TURNER N, TUTT A, ASHWORTH A: Hallmarks of ‘BRCAness’ in sporadic cancers. Nat. Rev. Cancer (2004) 4:814-819
  • MCCABE N, TURNER NC, LORD CJ et al.: Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition. Cancer Res. (2006) 66:8109-8115.
  • BRYANT HE, HELLEDAY T: Inhibition of poly (ADP-ribose) polymerase activates ATM which is required for subsequent homologous recombination repair. Nucleic Acids Res. (2006) 34:1685-1691.
  • LORD CJ, GARRETT MD, ASHWORTH A: Targeting the double-strand DNA break repair pathway as a therapeutic strategy. Clin. Cancer Res. (2006) 12:4463-4468.
  • PLUMMER ER: Inhibition of poly(ADP-ribose) polymerase in cancer. Curr. Opin. Pharmacol. (2006) 6:364-368.
  • PLUMMER ER: Poly(ADP-ribose) polymerase inhibitors: Clinical update. Eur. J. Cancer (2006) 4:141.
  • RATNAM K, LOW JA: Current development of clinical inhibitors of poly(ADP-ribose) polymerase in oncology. Clin. Cancer Res. (2007) 13:1383-1388.
  • WARD JF: The yield of DNA double-strand breaks produced intracellularly by ionizing radiation: a review. Int. J. Radiat. Biol. (1990) 57:1141-1150.
  • BURMA S, CHEN BPC, CHEN DJ: Role of non-homologous end joining (NHEJ) in maintaining genomic integrity. DNA Repair (2006) 5:1042-1048
  • OLIVE P L: The role of DNA single- and double-strand breaks in cell killing by ionizing radiation. Radiat. Res. (1998) 150:S42-S51.
  • ROTHKAMM K, KRUGER I, THOMPSON LH, LOBRICH M: Pathways of DNA double-strand break repair during the mammalian cell cycle. Mol. Cell. Biol. (2003) 23:5706-5715.
  • SMITH GC, JACKSON SP: The DNA-dependent protein kinase. Genes Dev. (1999) 13:916-934.
  • AHNESORG P, SMITH P, JACKSON SP: XLF interacts with the XRCC4-DNA ligase IV complex to promote DNA nonhomologous end-joining. Cell (2006) 124:301-313.
  • LEES-MILLER SP, MEEK K: Repair of DNA double strand breaks by non-homologous end joining. Biochimie (2003) 85:1161-1173.
  • JEGGO PA, CALDECOTT K, PIDSLEY S, BANKS GR: Sensitivity of Chinese hamster ovary mutants defective in DNA double strand break repair to topoisomerase II inhibitors. Cancer Res. (1989) 49:7057-7063.
  • TANAKA T, YAMAGAMI T, OKA Y, NOMURA T, SUGIYAMA H: The scid mutation in mice causes defects in the repair system for both double-strand DNA breaks and DNA cross-links. Mutat. Res. (1993) 288:277-280.
  • IZZARD RA, JACKSON SP, SMITH GC: Competitive and noncompetitive inhibition of the DNA-dependent protein kinase. Cancer Res. (1999) 59:2581-2586.
  • PRICE BD, YOUMELL MB: The phosphatidylinositol 3-kinase inhibitor wortmannin sensitizes murine fibroblasts and human tumor cells to radiation and blocks induction of p53 following DNA damage. Cancer Res. (1996) 56:246-250.
  • BOULTON S, KYLE S, DURKACZ BW: Mechanisms of enhancement of cytotoxicity in etoposide and ionising radiation-treated cells by the protein kinase inhibitor wortmannin. Eur. J. Cancer (2000) 36:535-541.
  • ROSENZWEIG KE, YOUMELL MB, PALAYOOR ST, PRICE BD: Radiosensitization of human tumor cells by the phosphatidylinositol3-kinase inhibitors wortmannin and LY294002 correlates with inhibition of DNA-dependent protein kinase and prolonged G2-M delay. Clin. Cancer Res. (1997) 3:1149-1156.
  • KRUSZEWSKI M, WOJEWODZKA M, IWANENKO T, SZUMIEL I, OKUYAMA A: Differential inhibitory effect of OK-1035 on DNA repair in L5178Y murine lymphoma sublines with functional or defective repair of double strand breaks. Mutat. Res. (1998) 409:31-36.
  • ISMAIL IH, MARTENSSON S, MOSHINSKY D et al.: SU11752 inhibits the DNA-dependent protein kinase and DNA double-strand break repair resulting in ionizing radiation sensitization. Oncogene (2004) 23:873-882.
  • WILLMORE E, DE CAUX S, SUNTER NJ et al.: A novel DNA-dependent protein kinase inhibitor, NU7026:potentiates the cytotoxicity of topoisomerase II poisons used in the treatment of leukemia. Blood (2004) 103:4659-4665.
  • HARDCASTLE IR, COCKCROFT X, CURTIN NJ et al.: Discovery of potent chromen-4-one inhibitors of the DNA-dependent protein kinase (DNA-PK) using a small-molecule library approach. J. Med. Chem. (2005) 48:7829-7846.
  • LEAHY JJ, GOLDING BT, GRIFFIN RJ et al.: Identification of a highly potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor (NU7441) by screening of chromenone libraries. Bioorg. Med. Chem. Lett. (2004) 14:6083-6087.
  • ZHAO Y, THOMAS HD, BATEY MA et al.: Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441. Cancer Res. (2006) 66:5354-5362.
  • KASHISHIAN A, DOUANGPANYA H, CLARK D et al.: DNA-dependent protein kinase inhibitors as drug candidates for the treatment of cancer. Mol. Cancer Ther. (2003) 2:1257-1264.
  • SHINOHARA ET, GENG L, TAN J et al.: DNA-dependent protein kinase is a molecular target for the development of noncytotoxic radiation-sensitizing drugs. Cancer Res. (2005) 65:4987-4992.
  • KENNEDY RD, D’ANDREA AD: DNA repair pathways in clinical practice: lessons from paediatric cancer susceptibility syndromes. J. Clin. Oncol. (2006) 24:3799-3808.
  • KAELIN W: The concept of synthetic lethality in the context of anticancer therapy. Nat. Rev. Cancer (2005) 5:689-698.

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