Breaking the DNA damage response to improve cervical cancer treatment

Cancer Treatment Reviews

Volumn 42, Issue , 2016, Pages 30-40

  Wieringa, Hylke W ^a   van der Zee, Ate G J ^a   de Vries, Elisabeth G E ^a   van Vugt, Marcel A T M ^a  

^a UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

Author keywords

Cervical cancer; Cisplatin; DDR inhibitors; DNA damage response; Radiotherapy

Indexed keywords

2 MORPHOLINO 6 (1 THIANTHRENYL) 4 PYRANONE; 5 (3 FLUOROPHENYL) N (3 PIPERIDINYL) 3 UREIDO 2 THIOPHENECARBOXAMIDE; 7 HYDROXYSTAUROSPORINE; ATM PROTEIN; ATR PROTEIN; AZ 20; AZD 6738; CC 115; CHECKPOINT KINASE 1; CHECKPOINT KINASE 2; CISPLATIN; CP 466722; DACTOLISIB; ETP 46464; KU 59403; KU 60019; KU 60648; MITOGEN ACTIVATED PROTEIN KINASE P38; NU 6027; NU 7026; NU 7441; PROTEIN KINASE INHIBITOR; PROTEIN SERINE THREONINE KINASE INHIBITOR; RABUSERTIB; SCHIZANDRIN B; UNCLASSIFIED DRUG; UNINDEXED DRUG; VE 821; VE 822; VX 970; WORTMANNIN; ANTINEOPLASTIC AGENT; DNA; ONCOPROTEIN; TUMOR PROTEIN; TUMOR SUPPRESSOR PROTEIN;

CANCER RADIOTHERAPY; CANCER THERAPY; CELL CYCLE CHECKPOINT; DNA DAMAGE; DNA DAMAGE RESPONSE; DNA REPAIR; DOUBLE STRANDED DNA BREAK; DRUG CYTOTOXICITY; DRUG TARGETING; HUMAN; NONHUMAN; PAPILLOMAVIRUS INFECTION; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); RADIOSENSITIZATION; REVIEW; SIGNAL TRANSDUCTION; SOMATIC MUTATION; SYSTEMATIC REVIEW; UTERINE CERVIX CANCER; WART VIRUS; ANTAGONISTS AND INHIBITORS; APOPTOSIS; CARCINOMA, SQUAMOUS CELL; CHEMORADIOTHERAPY; DRUG EFFECTS; DRUG RESISTANCE; FEMALE; GENE; GENE EXPRESSION REGULATION; GENETICS; MOLECULARLY TARGETED THERAPY; MUTATION; PAPILLOMAVIRIDAE; PAPILLOMAVIRUS INFECTIONS; PHYSIOLOGY; RADIATION RESPONSE; RADIATION TOLERANCE; TREATMENT FAILURE; UTERINE CERVICAL NEOPLASMS; VIROLOGY;

ANTINEOPLASTIC AGENTS; APOPTOSIS; CARCINOMA, SQUAMOUS CELL; CHEMORADIOTHERAPY; CISPLATIN; DNA BREAKS, DOUBLE-STRANDED; DNA DAMAGE; DNA REPAIR; DNA, NEOPLASM; DRUG RESISTANCE, NEOPLASM; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE EXPRESSION REGULATION, VIRAL; GENES, CDC; HUMANS; MOLECULAR TARGETED THERAPY; MUTATION; NEOPLASM PROTEINS; ONCOGENE PROTEINS, VIRAL; PAPILLOMAVIRIDAE; PAPILLOMAVIRUS INFECTIONS; PROTEIN KINASE INHIBITORS; RADIATION TOLERANCE; SIGNAL TRANSDUCTION; TREATMENT FAILURE; TUMOR SUPPRESSOR PROTEINS; UTERINE CERVICAL NEOPLASMS;

EID: 84955200083     PISSN: 03057372     EISSN: 15321967     Source Type: Journal    
DOI: 10.1016/j.ctrv.2015.11.008     Document Type: Review

References (150)

1. Ferlay J., Shin H.R., Bray F., Forman D., Mathers C., Parkin D.M. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 2010, 127:2893-2917.
2. Quinn M.A., Benedet J.L., Odicino F., Maisonneuve P., Beller U., Creasman W.T., et al. Carcinoma of the cervix uteri. FIGO 26th annual report on the results of treatment in gynecological cancer. Int J Gynaecol Obstet 2006, 95(Suppl. 1):S43-S103.
3. Rose P.G., Bundy B.N., Watkins E.B., Thigpen J.T., Deppe G., Maiman M.A., et al. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med 1999, 340:1144-1153.
4. Jackson S.P., Bartek J. The DNA-damage response in human biology and disease. Nature 2009, 461:1071-1078.
5. Hegi M.E., Diserens A.C., Gorlia T., Hamou M.F., de Tribolet N., Weller M., et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005, 352:997-1003.
6. Bryant H.E., Schultz N., Thomas H.D., Parker K.M., Flower D., Lopez E., et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 2005, 434:913-917.
7. Farmer H., McCabe N., Lord C.J., Tutt A.N.J., Johnson D.A., Richardson T.B., et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 2005, 434:917-921.
8. Fong P.C., Boss D.S., Yap T.A., Tutt A., Wu P., Mergui-Roelvink M., et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med 2009, 361:123-134.
9. Kelland L.R., Edwards S.M., Steel G.G. Induction and rejoining of DNA double-strand breaks in human cervix carcinoma cell lines of differing radiosensitivity. Radiat Res 1988, 116:526-538.
10. Wilson C.R., Davidson S.E., Margison G.P., Jackson S.P., Hendry J.H., West C.M. Expression of Ku70 correlates with survival in carcinoma of the cervix. Br J Cancer 2000, 83:1702-1706.
11. Doll C.M., Aquino-Parsons C., Pintilie M., Klimowicz A.C., Petrillo S.K., Milosevic M., et al. The significance of tumoral ERCC1 status in patients with locally advanced cervical cancer treated with chemoradiation therapy: a multicenter clinicopathologic analysis. Int J Radiat Oncol Biol Phys 2013, 85:721-727.
12. Walboomers J.M., Jacobs M.V., Manos M.M., Bosch F.X., Kummer J.A., Shah K.V., et al. Human papillomavirus is a necessary cause of invasive cervical cancer worldwide. J Pathol 1999, 189:12-19.
13. von Knebel Doeberitz M., Rittmüller C., zur Hausen H., Dürst M. Inhibition of tumorigenicity of cervical cancer cells in nude mice by HPV E6-E7 anti-sense RNA. Int J Cancer 1992, 51:831-834.
14. Dyson N., Howley P.M., Münger K., Harlow E. The human papilloma virus-16 E7 oncoprotein is able to bind to the retinoblastoma gene product. Science 1989, 243:934-937.
15. Werness B.A., Levine A.J., Howley P.M. Association of human papillomavirus types 16 and 18 E6 proteins with p53. Science 1990, 248:76-79.
16. Moody C.A., Laimins L.A. Human papillomavirus oncoproteins: pathways to transformation. Nat Rev Cancer 2010, 10:550-560.
17. Rieckmann T., Tribius S., Grob T.J., Meyer F., Busch C.-J., Petersen C., et al. HNSCC cell lines positive for HPV and p16 possess higher cellular radiosensitivity due to an impaired DSB repair capacity. Radiother Oncol 2013, 107:242-246.
18. Seiwert T.Y., Zuo Z., Keck M.K., Khattri A., Pedamallu C.S., Stricker T., et al. Integrative and comparative genomic analysis of HPV-positive and HPV-negative head and neck squamous cell carcinomas. Clin Cancer Res 2015, 21:632-641.
19. Hufbauer M., Cooke J., van der Horst G.T.J., Pfister H., Storey A., Akgül B. Human papillomavirus mediated inhibition of DNA damage sensing and repair drives skin carcinogenesis. Mol Cancer 2015, 14:183.
20. Park J.W., Nickel K.P., Torres A.D., Lee D., Lambert P.F., Kimple R.J. Human papillomavirus type 16 E7 oncoprotein causes a delay in repair of DNA damage. Radiother Oncol 2014, 113:337-344.
21. Wallace N.A., Robinson K., Howie H.L., Galloway D.A. β-HPV 5 and 8 E6 disrupt homology dependent double strand break repair by attenuating BRCA1 and BRCA2 expression and foci formation. PLoS Pathog 2015, 11:e1004687.
22. Iftner T., Elbel M., Schopp B., Hiller T., Loizou J.I., Caldecott K.W., et al. Interference of papillomavirus E6 protein with single-strand break repair by interaction with XRCC1. EMBO J 2002, 21:4741-4748.
23. Shin K.-H., Ahn J.H., Kang M.K., Lim P.K., Yip F.K., Baluda M.A., et al. HPV-16 E6 oncoprotein impairs the fidelity of DNA end-joining via p53-dependent and -independent pathways. Int J Oncol 2006, 28:209-215.
24. Ojesina A.I., Lichtenstein L., Freeman S.S., Pedamallu C.S., Imaz-Rosshandler I., Pugh T.J., et al. Landscape of genomic alterations in cervical carcinomas. Nature 2014, 506:371-375.
25. Tang K.-W., Alaei-Mahabadi B., Samuelsson T., Lindh M., Larsson E. The landscape of viral expression and host gene fusion and adaptation in human cancer. Nat Commun 2013, 4:2513.
26. Schiffman M., Castle P.E., Jeronimo J., Rodriguez A.C., Wacholder S. Human papillomavirus and cervical cancer. Lancet 2007, 370:890-907.
27. Smith J.S., Lindsay L., Hoots B., Keys J., Franceschi S., Winer R., et al. Human papillomavirus type distribution in invasive cervical cancer and high-grade cervical lesions: a meta-analysis update. Int J Cancer 2007, 121:621-632.
28. Thomas M., Narayan N., Pim D., Tomaić V., Massimi P., Nagasaka K., et al. Human papillomaviruses, cervical cancer and cell polarity. Oncogene 2008, 27:7018-7030.
29. Doorbar J., Quint W., Banks L., Bravo I.G., Stoler M., Broker T.R., et al. The biology and life-cycle of human papillomaviruses. Vaccine 2012, 30(Suppl. 5):F55-F70.
30. Fehrmann F., Laimins L.A. Human papillomaviruses: targeting differentiating epithelial cells for malignant transformation. Oncogene 2003, 22:5201-5207.
31. Münger K., Werness B.A., Dyson N., Phelps W.C., Harlow E., Howley P.M. Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product. EMBO J 1989, 8:4099-4105.
32. Khleif S.N., DeGregori J., Yee C.L., Otterson G.A., Kaye F.J., Nevins J.R., et al. Inhibition of cyclin D-CDK4/CDK6 activity is associated with an E2F-mediated induction of cyclin kinase inhibitor activity. Proc Natl Acad Sci USA 1996, 93:4350-4354.
33. Jones D.L., Münger K. Analysis of the p53-mediated G1 growth arrest pathway in cells expressing the human papillomavirus type 16 E7 oncoprotein. J Virol 1997, 71:2905-2912.
34. Bartkova J., Horejsí Z., Koed K., Krämer A., Tort F., Zieger K., et al. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 2005, 434:864-870.
35. Gorgoulis V.G., Vassiliou V.F., Karakaidos P., Zacharatos P., Kotsinas A., Liloglou T., et al. Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature 2005, 434:907-913.
36. Kastan M.B., Bartek J. Cell-cycle checkpoints and cancer. Nature 2004, 432:316-323.
37. Vogelstein B., Lane D., Levine A.J. Surfing the p53 network. Nature 2000, 408:307-310.
38. Bester A.C., Roniger M., Oren Y.S., Im M.M., Sarni D., Chaoat M., et al. Nucleotide deficiency promotes genomic instability in early stages of cancer development. Cell 2011, 145:435-446.
39. Zur Hausen H. Immortalization of human cells and their malignant conversion by high risk human papillomavirus genotypes. Semin Cancer Biol 1999, 9:405-411.
40. Forbes S.A., Beare D., Gunasekaran P., Leung K., Bindal N., Boutselakis H., et al. COSMIC: exploring the world's knowledge of somatic mutations in human cancer. Nucleic Acids Res 2014, 43:D805-D811.
41. Crook T., Wrede D., Tidy J.A., Mason W.P., Evans D.J., Vousden K.H. Clonal p53 mutation in primary cervical cancer: association with human-papillomavirus-negative tumours. Lancet 1992, 339:1070-1073.
42. McIntyre J.B., Wu J.S., Craighead P.S., Phan T., Köbel M., Lees-Miller S.P., et al. PIK3CA mutational status and overall survival in patients with cervical cancer treated with radical chemoradiotherapy. Gynecol Oncol 2013, 128:409-414.
43. Wingo S.N., Gallardo T.D., Akbay E.A., Liang M.C., Contreras C.M., Boren T., et al. Somatic LKB1 mutations promote cervical cancer progression. PLoS ONE 2009, 4:e5137.
44. Wright A.A., Howitt B.E., Myers A.P., Dahlberg S.E., Palescandolo E., van Hummelen P., et al. Oncogenic mutations in cervical cancer: genomic differences between adenocarcinomas and squamous cell carcinomas of the cervix. Cancer 2013, 119:3776-3783.
45. Hermeking H., Lengauer C., Polyak K., He T.C., Zhang L., Thiagalingam S., et al. 14-3-3 sigma is a p53-regulated inhibitor of G2/M progression. Mol Cell 1997, 1:3-11.
46. Khanna K.K., Jackson S.P. DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet 2001, 27:247-254.
47. Uziel T., Lerenthal Y., Moyal L., Andegeko Y., Mittelman L., Shiloh Y. Requirement of the MRN complex for ATM activation by DNA damage. EMBO J 2003, 22:5612-5621.
48. Bakkenist C.J., Kastan M.B. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 2003, 421:499-506.
49. Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R., Hurov K.E., Luo J., et al. ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 2007, 316:1160-1166.
50. Ahn J.Y., Schwarz J.K., Piwnica-Worms H., Canman C.E. Threonine 68 phosphorylation by ataxia telangiectasia mutated is required for efficient activation of Chk2 in response to ionizing radiation. Cancer Res 2000, 60:5934-5936.
51. Matsuoka S., Huang M., Elledge S.J. Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science 1998, 282:1893-1897.
52. el-Deiry W.S., Tokino T., Velculescu V.E., Levy D.B., Parsons R., Trent J.M., et al. WAF1, a potential mediator of p53 tumor suppression. Cell 1993, 75:817-825.
53. Harper J.W., Adami G.R., Wei N., Keyomarsi K., Elledge S.J. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell 1993, 75:805-816.
54. Zeman M.K., Cimprich K.A. Causes and consequences of replication stress. Nat Cell Biol 2014, 16:2-9.
55. Mailand N., Falck J., Lukas C., Syljuâsen R.G., Welcker M., Bartek J., et al. Rapid destruction of human Cdc25A in response to DNA damage. Science 2000, 288:1425-1429.
56. López-Contreras A.J., Fernandez-Capetillo O. The ATR barrier to replication-born DNA damage. DNA Repair (Amst) 2010, 9:1249-1255.
57. Schoppy D.W., Ragland R.L., Gilad O., Shastri N., Peters A.A., Murga M., et al. Oncogenic stress sensitizes murine cancers to hypomorphic suppression of ATR. J Clin Invest 2012, 122:241-252.
58. López-Contreras A.J., Gutierrez-Martinez P., Specks J., Rodrigo-Perez S., Fernandez-Capetillo O. An extra allele of Chk1 limits oncogene-induced replicative stress and promotes transformation. J Exp Med 2012, 209:455-461.
59. Tibbetts R.S., Cortez D., Brumbaugh K.M., Scully R., Livingston D., Elledge S.J., et al. Functional interactions between BRCA1 and the checkpoint kinase ATR during genotoxic stress. Genes Dev 2000, 14:2989-3002.
60. Reinhardt H.C., Aslanian A.S., Lees J.A., Yaffe M.B. P53-deficient cells rely on ATM- and ATR-mediated checkpoint signaling through the p38MAPK/MK2 pathway for survival after DNA damage. Cancer Cell 2007, 11:175-189.
61. Kyriakis J.M., Avruch J. Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev 2001, 81:807-869.
62. Tanoue T., Maeda R., Adachi M., Nishida E. Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions. EMBO J 2001, 20:466-479.
63. Smith J.A., Poteet-Smith C.E., Lannigan D.A., Freed T.A., Zoltoski A.J., Sturgill T.W. Creation of a stress-activated p90 ribosomal S6 kinase. The carboxyl-terminal tail of the MAPK-activated protein kinases dictates the signal transduction pathway in which they function. J Biol Chem 2000, 275:31588-31593.
64. Raman M., Earnest S., Zhang K., Zhao Y., Cobb M.H. TAO kinases mediate activation of p38 in response to DNA damage. EMBO J 2007, 26:2005-2014.
65. Manke I.A., Nguyen A., Lim D., Stewart M.Q., Elia A.E.H., Yaffe M.B. MAPKAP kinase-2 is a cell cycle checkpoint kinase that regulates the G2/M transition and S phase progression in response to UV irradiation. Mol Cell 2005, 17:37-48.
66. Reinhardt H.C., Hasskamp P., Schmedding I., Morandell S., van Vugt M.A.T.M., Wang X., et al. DNA damage activates a spatially distinct late cytoplasmic cell-cycle checkpoint network controlled by MK2-mediated RNA stabilization. Mol Cell 2010, 40:34-49.
67. Ma Y., Lu H., Tippin B., Goodman M.F., Shimazaki N., Koiwai O., et al. A biochemically defined system for mammalian nonhomologous DNA end joining. Mol Cell 2004, 16:701-713.
68. Lieber M.R., Lu H., Gu J., Schwarz K. Flexibility in the order of action and in the enzymology of the nuclease, polymerases, and ligase of vertebrate non-homologous DNA end joining: relevance to cancer, aging, and the immune system. Cell Res 2008, 18:125-133.
69. Sung P., Klein H. Mechanism of homologous recombination: mediators and helicases take on regulatory functions. Nat Rev Mol Cell Biol 2006, 7:739-750.
70. D'Andrea A.D., Grompe M. The Fanconi anaemia/BRCA pathway. Nat Rev Cancer 2003, 3:23-34.
71. Wang W. Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins. Nat Rev Genet 2007, 8:735-748.
72. Duensing S., Münger K. The human papillomavirus type 16 E6 and E7 oncoproteins independently induce numerical and structural chromosome instability. Cancer Res 2002, 62:7075-7082.
73. Havre P.A., Yuan J., Hedrick L., Cho K.R., Glazer P.M. P53 inactivation by HPV16 E6 results in increased mutagenesis in human cells. Cancer Res 1995, 55:4420-4424.
74. Deng W., Tsao S.W., Guan X.-Y., Cheung A.L.M. Pericentromeric regions are refractory to prompt repair after replication stress-induced breakage in HPV16 E6E7-expressing epithelial cells. PLoS ONE 2012, 7:e48576.
75. Chen B., Simpson D.A., Zhou Y., Mitra A., Mitchell D.L., Cordeiro-Stone M., et al. Human papilloma virus type16 E6 deregulates CHK1 and sensitizes human fibroblasts to environmental carcinogens independently of its effect on p53. Cell Cycle 2009, 8:1775-1787.
76. Giampieri S., Storey A. Repair of UV-induced thymine dimers is compromised in cells expressing the E6 protein from human papillomaviruses types 5 and 18. Br J Cancer 2004, 90:2203-2209.
77. Wallace N.A., Robinson K., Howie H.L., Galloway D.A. HPV 5 and 8 E6 abrogate ATR activity resulting in increased persistence of UVB induced DNA damage. PLoS Pathog 2012, 8:e1002807.
78. Ford J.M., Baron E.L., Hanawalt P.C. Human fibroblasts expressing the human papillomavirus E6 gene are deficient in global genomic nucleotide excision repair and sensitive to ultraviolet irradiation. Cancer Res 1998, 58:599-603.
79. Ferguson B.E., Oh D.H. Proficient global nucleotide excision repair in human keratinocytes but not in fibroblasts deficient in p53. Cancer Res 2005, 65:8723-8729.
80. Srivenugopal K.S., Ali-Osman F. The DNA repair protein, O(6)-methylguanine-DNA methyltransferase is a proteolytic target for the E6 human papillomavirus oncoprotein. Oncogene 2002, 21:5940-5945.
81. McHugh P.J., Spanswick V.J., Hartley J.A. Repair of DNA interstrand crosslinks: molecular mechanisms and clinical relevance. Lancet Oncol 2001, 2:483-490.
82. Doles J., Oliver T.G., Cameron E.R., Hsu G., Jacks T., Walker G.C., et al. Suppression of Rev3, the catalytic subunit of Pol, sensitizes drug-resistant lung tumors to chemotherapy. Proc Natl Acad Sci USA 2010, 107:20786-20791.
83. Savitsky K., Bar-Shira A., Gilad S., Rotman G., Ziv Y., Vanagaite L., et al. A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 1995, 268:1749-1753.
84. Shiloh Y. ATM and related protein kinases: safeguarding genome integrity. Nat Rev Cancer 2003, 3:155-168.
85. Riballo E., Kühne M., Rief N., Doherty A., Smith G.C.M., Recio M.J., et al. A pathway of double-strand break rejoining dependent upon ATM, Artemis, and proteins locating to gamma-H2AX foci. Mol Cell 2004, 16:715-724.
86. Cremona C.A., Behrens A. ATM signalling and cancer. Oncogene 2014, 33:3351-3360.
87. Cerami E., Gao J., Dogrusoz U., Gross B.E., Sumer S.O., Aksoy B.A., et al. The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data. Cancer Discov 2012, 2:401-404.
88. Gao J., Aksoy B.A., Dogrusoz U., Dresdner G., Gross B., Sumer S.O., et al. Integrative analysis of complex cancer genomics and clinical profiles using the cBioPortal. Sci Signal 2013, 6:pl1.
89. Roossink F., Wieringa H.W., Noordhuis M.G., Hoor ten K.A., Kok M., Slagter-Menkema L., et al. The role of ATM and 53BP1 as predictive markers in cervical cancer. Int J Cancer 2012, 131:2056-2066.
90. Powell S.N., DeFrank J.S., Connell P., Eogan M., Preffer F., Dombkowski D., et al. Differential sensitivity of p53(-) and p53(+) cells to caffeine-induced radiosensitization and override of G2 delay. Cancer Res 1995, 55:1643-1648.
91. Kelland L.R., Steel G.G. Modification of radiation dose-rate sparing effects in a human carcinoma of the cervix cell line by inhibitors of DNA repair. Int J Radiat Biol 1988, 54:229-244.
92. Sarkaria J.N., Busby E.C., Tibbetts R.S., Roos P., Taya Y., Karnitz L.M., et al. Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine. Cancer Res 1999, 59:4375-4382.
93. Price B.D., Youmell M.B. 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.
94. Sarkaria J.N., Tibbetts R.S., Busby E.C., Kennedy A.P., Hill D.E., Abraham R.T. Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing agent wortmannin. Cancer Res 1998, 58:4375-4382.
95. Hickson I., Zhao Y., Richardson C.J., Green S.J., Martin N.M.B., Orr A.I., et al. Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM. Cancer Res 2004, 64:9152-9159.
96. Golding S.E., Rosenberg E., Valerie N., Hussaini I., Frigerio M., Cockcroft X.F., et al. Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion. Mol Cancer Ther 2009, 8:2894-2902.
97. Batey M.A., Zhao Y., Kyle S., Richardson C., Slade A., Martin N.M.B., et al. Preclinical evaluation of a novel ATM inhibitor, KU59403, in vitro and in vivo in p53 functional and dysfunctional models of human cancer. Mol Cancer Ther 2013, 12:959-967.
98. Biddlestone-Thorpe L., Sajjad M., Rosenberg E., Beckta J.M., Valerie N.C.K., Tokarz M., et al. ATM kinase inhibition preferentially sensitizes p53-mutant glioma to ionizing radiation. Clin Cancer Res 2013, 19:3189-3200.
99. Rainey M.D., Charlton M.E., Stanton R.V., Kastan M.B. Transient inhibition of ATM kinase is sufficient to enhance cellular sensitivity to ionizing radiation. Cancer Res 2008, 68:7466-7474.
100. de Klein A., Muijtjens M., van Os R., Verhoeven Y., Smit B., Carr A.M., et al. Targeted disruption of the cell-cycle checkpoint gene ATR leads to early embryonic lethality in mice. Curr Biol 2000, 10:479-482.
101. Nishida H., Tatewaki N., Nakajima Y., Magara T., Ko K.M., Hamamori Y., et al. Inhibition of ATR protein kinase activity by schisandrin B in DNA damage response. Nucleic Acids Res 2009, 37:5678-5689.
102. Charrier J.D., Durrant S.J., Golec J.M.C., Kay D.P., Knegtel R.M.A., MacCormick S., et al. Discovery of potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase as potential anticancer agents. J Med Chem 2011, 54:2320-2330.
103. Gamper A.M., Rofougaran R., Watkins S.C., Greenberger J.S., Beumer J.H., Bakkenist C.J. ATR kinase activation in G1 phase facilitates the repair of ionizing radiation-induced DNA damage. Nucleic Acids Res 2013, 41:10334-10344.
104. Toledo L.I., Murga M., Zur R., Soria R., Rodriguez A., Martinez S., et al. A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations. Nat Struct Mol Biol 2011, 18:721-727.
105. Maira S.M., Stauffer F., Brueggen J., Furet P., Schnell C., Fritsch C., et al. Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ther 2008, 7:1851-1863.
106. Arris C.E., Boyle F.T., Calvert A.H., Curtin N.J., Endicott J.A., Garman E.F., et al. Identification of novel purine and pyrimidine cyclin-dependent kinase inhibitors with distinct molecular interactions and tumor cell growth inhibition profiles. J Med Chem 2000, 43:2797-2804.
107. Peasland A., Wang L.Z., Rowling E., Kyle S., Chen T., Hopkins A., et al. Identification and evaluation of a potent novel ATR inhibitor, NU6027, in breast and ovarian cancer cell lines. Br J Cancer 2011, 105:372-381.
108. Foote K.M., Blades K., Cronin A., Fillery S., Guichard S.S., Hassall L., et al. Discovery of 4-(4-[(3R)-3-methylmorpholin-4-yl]-6-[1-(methylsulfonyl)cyclopropyl]pyrimidin-2-yl)-1H-indole (AZ20): a potent and selective inhibitor of ATR protein kinase with monotherapy in vivo antitumor activity. J Med Chem 2013, 56:2125-2138.
109. Reaper P.M., Griffiths M.R., Long J.M., Charrier J.D., MacCormick S., Charlton P.A., et al. Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR. Nat Chem Biol 2011, 7:428-430.
110. Fokas E., Prevo R., Pollard J.R., Reaper P.M., Charlton P.A., Cornelissen B., et al. Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation. Cell Death Dis 2012, 3. e441-e410.
111. Kurimasa A., Kumano S., Boubnov N.V., Story M.D., Tung C.S., Peterson S.R., et al. Requirement for the kinase activity of human DNA-dependent protein kinase catalytic subunit in DNA strand break rejoining. Mol Cell Biol 1999, 19:3877-3884.
112. Jeggo P.A., Caldecott K., Pidsley S., Banks G.R. Sensitivity of Chinese hamster ovary mutants defective in DNA double strand break repair to topoisomerase II inhibitors. Cancer Res 1989, 49:7057-7063.
113. Beskow C., Skikuniene J., Holgersson A., Nilsson B., Lewensohn R., Kanter L., et al. Radioresistant cervical cancer shows upregulation of the NHEJ proteins DNA-PKcs, Ku70 and Ku86. Br J Cancer 2009, 101:816-821.
114. Collis S.J., DeWeese T.L., Jeggo P.A., Parker A.R. The life and death of DNA-PK. Oncogene 2005, 24:949-961.
115. Leahy J.J.J., Golding B.T., Griffin R.J., Hardcastle I.R., Richardson C., Rigoreau L., 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.
116. Willmore E., de Caux S., Sunter N.J., Tilby M.J., Jackson G.H., Austin C.A., 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.
117. Zhao Y., Thomas H.D., Batey M.A., Cowell I.G., Richardson C.J., Griffin R.J., et al. Preclinical evaluation of a potent novel DNA-dependent protein kinase inhibitor NU7441. Cancer Res 2006, 66:5354-5362.
118. Zhou X., Zhang X., Xie Y., Tanaka K., Wang B., Zhang H. DNA-PKcs inhibition sensitizes cancer cells to carbon-ion irradiation via telomere capping disruption. PLoS ONE 2013, 8:e72641.
119. Shang Z.F., Huang B., Xu Q.Z., Zhang S.M., Fan R., Liu X.D., et al. Inactivation of DNA-dependent protein kinase leads to spindle disruption and mitotic catastrophe with attenuated checkpoint protein 2 phosphorylation in response to DNA damage. Cancer Res 2010, 70:3657-3666.
120. An J., Huang Y.C., Xu Q.Z., Zhou L.J., Shang Z.F., Huang B., et al. DNA-PKcs plays a dominant role in the regulation of H2AX phosphorylation in response to DNA damage and cell cycle progression. BMC Mol Biol 2010, 11:18.
121. Munck J.M., Batey M.A., Zhao Y., Jenkins H., Richardson C.J., Cano C., et al. Chemosensitization of cancer cells by KU-0060648, a dual inhibitor of DNA-PK and PI-3K. Mol Cancer Ther 2012, 11:1789-1798.
122. Zhang Y., Fan S., Meng Q., Ma Y., Katiyar P., Schlegel R., et al. BRCA1 interaction with human papillomavirus oncoproteins. J Biol Chem 2005, 280:33165-33177.
123. Bindra R.S., Schaffer P.J., Meng A., Woo J., Måseide K., Roth M.E., et al. Down-regulation of Rad51 and decreased homologous recombination in hypoxic cancer cells. Mol Cell Biol 2004, 24:8504-8518.
124. Vaupel P., Thews O., Hoeckel M. Treatment resistance of solid tumors: role of hypoxia and anemia. Med Oncol 2001, 18:243-259.
125. Rockwell S. Oxygen delivery: implications for the biology and therapy of solid tumors. Oncol Res 1997, 9:383-390.
126. Matsuoka S., Rotman G., Ogawa A., Shiloh Y., Tamai K., Elledge S.J. Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro. Proc Natl Acad Sci USA 2000, 97:10389-10394.
127. Zhao H., Piwnica-Worms H. ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1. Mol Cell Biol 2001, 21:4129-4139.
128. Peng C.Y., Graves P.R., Thoma R.S., Wu Z., Shaw A.S., Piwnica-Worms H. Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216. Science 1997, 277:1501-1505.
129. Sørensen C.S., Hansen L.T., Dziegielewski J., Syljuåsen R.G., Lundin C., Bartek J., et al. The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair. Nat Cell Biol 2005, 7:195-201.
130. Zenvirt S., Kravchenko-Balasha N., Levitzki A. Status of p53 in human cancer cells does not predict efficacy of CHK1 kinase inhibitors combined with chemotherapeutic agents. Oncogene 2010, 29:6149-6159.
131. Beeharry N., Rattner J.B., Caviston J.P., Yen T. Centromere fragmentation is a common mitotic defect of S and G2 checkpoint override. Cell Cycle 2013, 12:1588-1597.
132. Chen Y., Chow J.P.H., Poon R.Y.C. Inhibition of Eg5 acts synergistically with checkpoint abrogation in promoting mitotic catastrophe. Mol Cancer Res 2012, 10:626-635.
133. Sommers G.M., Alfieri A.A. Multimodality therapy: radiation and continuous concomitant cis-platinum and PKC inhibition in a cervical carcinoma model. Cancer Invest 1998, 16:462-470.
134. Wagner J.M., Karnitz L.M. Cisplatin-induced DNA damage activates replication checkpoint signaling components that differentially affect tumor cell survival. Mol Pharmacol 2009, 76:208-214.
135. Bunch R.T., Eastman A. Enhancement of cisplatin-induced cytotoxicity by 7-hydroxystaurosporine (UCN-01), a new G2-checkpoint inhibitor. Clin Cancer Res 1996, 2:791-797.
136. Zhao H., Watkins J.L., Piwnica-Worms H. Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints. Proc Natl Acad Sci USA 2002, 99:14795-14800.
137. Ma C.X., Janetka J.W., Piwnica-Worms H. Death by releasing the breaks: CHK1 inhibitors as cancer therapeutics. Trends Mol Med 2011, 17:88-96.
138. Ma C.X., Ellis M.J.C., Petroni G.R., Guo Z., Cai S.R., Ryan C.E., et al. A phase II study of UCN-01 in combination with irinotecan in patients with metastatic triple negative breast cancer. Breast Cancer Res Treat 2013, 137:483-492.
139. Welch S., Hirte H.W., Carey M.S., Hotte S.J., Tsao M.S., Brown S., et al. UCN-01 in combination with topotecan in patients with advanced recurrent ovarian cancer: a study of the Princess Margaret Hospital Phase II consortium. Gynecol Oncol 2007, 106:305-310.
140. Li T., Christensen S.D., Frankel P.H., Margolin K.A., Agarwala S.S., Luu T., et al. A phase II study of cell cycle inhibitor UCN-01 in patients with metastatic melanoma: a California Cancer Consortium trial. Invest New Drugs 2012, 30:741-748.
141. Rini B.I., Weinberg V., Shaw V., Scott J., Bok R., Park J.W., et al. Time to disease progression to evaluate a novel protein kinase C inhibitor, UCN-01, in renal cell carcinoma. Cancer 2004, 101:90-95.
142. Fuse E., Tanii H., Kurata N., Kobayashi H., Shimada Y., Tamura T., et al. Unpredicted clinical pharmacology of UCN-01 caused by specific binding to human alpha1-acid glycoprotein. Cancer Res 1998, 58:3248-3253.
143. Zabludoff S.D., Deng C., Grondine M.R., Sheehy A.M., Ashwell S., Caleb B.L., et al. AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies. Mol Cancer Ther 2008, 7:2955-2966.
144. Morgan M.A., Parsels L.A., Zhao L., Parsels J.D., Davis M.A., Hassan M.C., et al. Mechanism of radiosensitization by the Chk1/2 inhibitor AZD7762 involves abrogation of the G2 checkpoint and inhibition of homologous recombinational DNA repair. Cancer Res 2010, 70:4972-4981.
145. Seto T., Esaki T., Hirai F., Arita S., Nosaki K., Makiyama A., et al. Phase I, dose-escalation study of AZD7762 alone and in combination with gemcitabine in Japanese patients with advanced solid tumours. Cancer Chemother Pharmacol 2013, 72:619-627.
146. Sausville E., LoRusso P., Carducci M., Carter J., Quinn M.F., Malburg L., et al. Phase I dose-escalation study of AZD7762, a checkpoint kinase inhibitor, in combination with gemcitabine in US patients with advanced solid tumors. Cancer Chemother Pharmacol 2014, 73:539-549.
147. King C., Diaz H., Barnard D., Barda D., Clawson D., Blosser W., et al. Characterization and preclinical development of LY2603618: a selective and potent Chk1 inhibitor. Invest New Drugs 2014, 32:213-226.
148. Bulavin D.V., Higashimoto Y., Popoff I.J., Gaarde W.A., Basrur V., Potapova O., et al. Initiation of a G2/M checkpoint after ultraviolet radiation requires p38 kinase. Nature 2001, 411:102-107.
149. Gurgis F.M.S., Ziaziaris W., Munoz L. Mitogen-activated protein kinase-activated protein kinase 2 in neuroinflammation, heat shock protein 27 phosphorylation, and cell cycle: role and targeting. Mol Pharmacol 2014, 85:345-356.
150. Halazonetis T.D., Gorgoulis V.G., Bartek J. An oncogene-induced DNA damage model for cancer development. Science 2008, 319:1352-1355.