Ataxia-telangiectasia mutated and the Mre11-Rad50-NBS1 complex: Promising targets for radiosensitization

Acta Medica Okayama

Volumn 66, Issue 2, 2012, Pages 83-92

  Kuroda, Shinji ^a,b   Urata, Yasuo ^c   Fujiwara, Toshiyoshi ^a  

^a OKAYAMA UNIVERSITY   (Japan)

^b UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^c National Institute of Infectious Diseases   (Japan)

Author keywords

Adenovirus; ATM (ataxia telangiectasia mutated); ElB55kDa; MRN (Mrell Rad50 NBSl) complex; Radiosensitization

Indexed keywords

ATM PROTEIN; CELL CYCLE PROTEIN; DNA BINDING PROTEIN; E1B55K PROTEIN, ADENOVIRUS; PROTEIN SERINE THREONINE KINASE; RADIOSENSITIZING AGENT; TUMOR SUPPRESSOR PROTEIN; VIRUS PROTEIN;

ATAXIA TELANGIECTASIA; CELL CYCLE CHECKPOINT; DNA DAMAGE; DNA REPAIR; GENETICS; HUMAN; METABOLISM; RADIATION EXPOSURE; REVIEW; SIGNAL TRANSDUCTION;

ATAXIA TELANGIECTASIA; CELL CYCLE CHECKPOINTS; CELL CYCLE PROTEINS; DNA DAMAGE; DNA REPAIR; DNA-BINDING PROTEINS; HUMANS; PROTEIN-SERINE-THREONINE KINASES; RADIATION-SENSITIZING AGENTS; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR PROTEINS; VIRAL PROTEINS;

ADENOVIRIDAE; ATAXIA TELANGIECTASIA;

EID: 84864746641     PISSN: 0386300X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (90)

1. Mendelsohn FA, Divino CM, Reis ED and Kerstein MD: Wound care after radiation therapy. Adv Skin Wound Care (2002) 15: 216-224.
2. Timmerman RD, Kavanagh BD, Cho LC, Papiez L and Xing L: Stereotactic body radiation therapy in multiple organ sites. J Clin Oncol (2007) 25: 947-952.
3. Bentzen SM, Harari PM and Bernier J: Exploitable mechanisms for combining drugs with radiation: concepts, achievements and future directions. Nat Clin Pract Oncol (2007) 4: 172-180.
4. Okunieff P, de BieJ, Dunphy EP, Terris DJ and Hockel M: Oxygen distributions partly explain the radiation response of human squamous cell carcinomas. Br J Cancer Suppl (1996) 27: S185-190.
5. Harrison LB, Chadha M, Hill RJ, Hu K and Shasha D: Impact of tumor hypoxia and anemia on radiation therapy outcomes. Oncol ogist (2002) 7: 492-508.
6. Varlotto J and Stevenson MA: Anemia, tumor hypoxemia, and the cancer patient. Int J Radiat Oncol Biol Phys (2005) 63: 25-36.
7. Overgaard J and Horsman MR: Modification of Hypoxia-lnduced Radioresistance in Tumors by the Use of Oxygen and Sensitizers. Semin Radiat Oncol (1996) 6: 10-21.
8. Krempler A, Deckbar D, Jeggo PA and Lobrich M: An imperfect G2M checkpoint contributes to chromosome instability following irradiation of S and G2 phase cells. Cell Cycle (2007) 6: 1682-1686.
9. Mimitou EP and Symington LS: DNA end resection: many nucleases make light work. DNA Repair (Amst) (2009) 8: 983-995.
10. Lamarche BJ, Orazio Nl and Weitzman MD: The MRN complex in double-strand break repair and telomere maintenance. FEBS Lett (2010) 584: 3682-3695.
11. Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, Kish JA, Kim HE, Cmelak AJ, Rotman M, Machtay M, Ensley JF, Chao KS, Schultz CJ, Lee N and Fu KK: Postoperative concurrent radiotherapy and chemotherapy for highrisk squamous-cell carcinoma of the head and neck. N Engl J Med (2004) 350: 1937-1944.
12. Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefebvre JL, Greiner RH, Giralt J, Maingon P, Rolland F, Bolla M, Cognetti F, Bourhis J, Kirkpatrick A and van Glabbeke M: Postoperative irra diation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med (2004) 350: 1945-1952.
13. Longley DB, Harkin DP and Johnston PG: 5-fluorouracil: mecha nisms of action and clinical strategies. Nat Rev Cancer (2003) 3: 330-338.
14. Spalding AC and Lawrence TS: New and emerging radiosensitizers and radioprotectors. Cancer Invest (2006) 24: 444-456.
15. Hermann RM, Rave-Frank M and Pradier O: Combining radiation with oxaliplatin: a review of experimental results. Cancer Radiother (2008) 12: 61-67.
16. Morgan MA, Parsels LA, Maybaum J and Lawrence TS: Improving gemcitabine-mediated radiosensitization using molecularly targeted therapy: a review. Clin Cancer Res (2008) 14: 6744-6750.
17. Wachters FM, van Putten JW, Maring JG, Zdzienicka MZ, Groen HJ and Kampinga HH: Selective targeting of homologous DNA recombination repair by gemcitabine. Int J Radiat Oncol Biol Phys (2003)57: 553-562.
18. Morgan MA, Parsels LA, Parsels JD, Mesiwala AK, Maybaum J and Lawrence TS: Role of checkpoint kinase 1 in preventing pre mature mitosis in response to gemcitabine. Cancer Res (2005) 65: 6835-6842.
19. Momm F, Kaden M, Tannock I, Schumacher M, Hasse J and Henke M: Dose escalation of gemcitabine concomitant with radia tion and cisplatin for nonsmall cell lung cancer: a phase 1-2study. Cancer (2010) 116: 4833-4839.
20. Cooke EW and Hazard L: Curative radiation therapy for pancreatic malignancies. Surg Clin North Am (2010) 90: 341-354.
21. Benasso M, Vigo V, Bacigalupo A, Ponzanelli A, Marcenaro M, Corvo R and Margarino G: A phase II trial of low-dose gemcitabine and radiation alternated to cisplatin and 5-fluorouracil: an active and manageable regimen for stage IV squamous cell carcinoma of the head and neck. Radiother Oncol (2008) 89: 44-50.
22. Milas L, Milas MM and Mason KA: Combination of taxanes with radiation: preclinical studies. Semin Radiat Oncol (1999) 9: 12-26.
23. Chen Y, Pandya K, Keng PP, Feins R, Raubertas R, Smudzin T, Rosenblatt J and Okunieff P: Schedule-dependent pulsed paclitaxel radiosensitization for thoracic malignancy. Am J Clin Oncol (2001) 24: 432-437.
24. Zhao J, Kim JE, Reed E and Li QQ: Molecular mechanism of antitumor activity of taxanes in lung cancer (Review). Int J Oncol(2005) 27: 247-256.
25. Lau D, Leigh B, Gandara D, Edelman M, Morgan R, Israel V, Lara P, Wilder R, Ryu J and Doroshow J: Twice-weekly paclitaxel and weekly carboplatin with concurrent thoracic radiation followed by carboplatin/paclitaxel consolidation for stage III non-small-cell lung cancer: a California Cancer Consortium phase II trial. J Clin Oncol (2001) 19: 442-447.
26. Tishler RB, Norris CM Jr, ColevasAD, Lamb CC, Karp D, Busse PM, Nixon A, Frankenthaler R, Lake-Willcutt B, Costello R, Case M and Posner MR: A Phase l/ll trial of concurrent docetaxel and radiation after induction chemotherapy in patients with poor prog nosis squamous cell carcinoma of the head and neck. Cancer (2002)95: 1472-1481.
27. Kleinberg L and Forastiere AA: Chemoradiation in the manage ment of esophageal cancer. J Clin Oncol (2007) 25: 4110-4117.
28. Chen AY, Chou R, Shih SJ, Lau D and Gandara D: Enhancement of radiotherapy with DNA topoisomerase l-targeted drugs. Crit Rev Oncol Hematol (2004) 50: 111-119.
29. Murphy BA: Topoisomerases in the treatment of metastatic or recurrent squamous carcinoma of the head and neck. Expert Opin Pharmacother (2005) 6: 85-92.
30. Llson DH, Bains M, Kelsen DP, O'Reilly E, Karpeh M, Coit D, Rusch V, Gonen M, Wilson K and Minsky BD: Phase I trial of escalating-dose irinotecan given weekly with cisplatin and concur rent radiotherapy in locally advanced esophageal cancer. J Clin Oncol (2003) 21: 2926-2932.
31. Takeda K, Negoro S, Tanaka M, Fukuda H, Nakagawa K, Kawahara M, Semba H, Kudoh S, Sawa T, Saijo N and Fukuoka M: A phase II study of cisplatin and irinotecan as induction che motherapy followed by concomitant thoracic radiotherapy with weekly low-dose irinotecan in unresectable, stage III, non-small cell lung cancer: JCOG 9706. Jpn J Clin Oncol (2011) 41: 25-31.
32. Feun L and Savaraj N: Topoisomerase I inhibitors for the treatment of brain tumors. Expert Rev Anticancer Ther (2008) 8: 707-716.
33. Zhukov NV and Tjulandin SA: Targeted therapy in the treatment of solid tumors: practice contradicts theory. Biochemistry (Mosc) (2008) 73: 605-618.
34. Press MF and Lenz HJ: EGFR, HER2 and VEGF pathways: validated targets for cancer treatment. Drugs (2007) 67: 2045-2075.
35. Janku F, Stewart DJ and Kurzrock R: Targeted therapy in non-small-cell lung cancer-is it becoming a reality? Nat Rev Clin Oncol (2010) 7: 401-414.
36. Camphausen K and Tofilon PJ: Inhibition of histone deacetylation: a strategy for tumor radiosensitization. J Clin Oncol (2007) 25: 4051-4056.
37. Almenara J, Rosato R and Grant S: Synergistic induction of mitochondrial damage and apoptosis in human leukemia cells by flavopiridol and the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA). Leukemia (2002) 16: 1331-1343.
38. Marks PA: The clinical development of histone deacetylase inhibi tors as targeted anticancer drugs. Expert Opin Investig Drugs (2010) 19: 1049-1066.
39. Camphausen K, Burgan W, Cerra M, Oswald KA, Trepel JB, Lee MJ and Tofilon PJ: Enhanced radiation-induced cell killing and prolongation of gammaH2AX foci expression by the histone deacetylase inhibitor MS-275. Cancer Res (2004) 64: 316-321.
40. Munshi A, Kurland JF, Nishikawa T, Tanaka T, Hobbs ML, Tucker SL, Ismail S, Stevens C and Meyn RE: Histone deacety lase inhibitors radiosensitize human melanoma cells by suppress ing DNA repair activity. Clin Cancer Res (2005) 11: 4912-4922.
41. Ree AH, Dueland S, Folkvord S, Hole KH, Seierstad T, Johansen M, Abrahamsen TW and Flatmark K: Vorinostat, a his tone deacetylase inhibitor, combined with pelvic palliative radio therapy for gastrointestinal carcinoma: the Pelvic Radiation and Vorinostat (PRAVO) phase 1 study. Lancet Oncol (2010) 11: 459-464.
42. Shabason JE, Tofilon PJ and Camphausen K: Grand Rounds at the National Institutes of Health: HDAC Inhibitors as RadiationModifiers, from Bench to Clinic. J Cell Mol Med (2011).
43. Noel G, Giocanti N, Fernet M, Megnin-Chanet F and Favaudon V: Poly (ADP-ribose) polymerase (PARP-1) is not involved in DNA double-strand break recovery. BMC Cell Biol (2003) 4: 7.
44. Schultz N, Lopez E, Saleh-Gohari N and Helleday T: Poly (ADP-ribose) polymerase (PARP-1) has a controlling role in homologous recombination. Nucleic Acids Res (2003) 31: 4959-4964.
45. Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, Martin NM, Jackson SP, Smith GC and Ashworth A: Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strat egy. Nature (2005) 434: 917-921.
46. Loser DA, Shibata A, Shibata AK, Woodbine LJ, Jeggo PA and Chalmers AJ: Sensitization to radiation and alkylating agents by inhibitors of poly (ADP-ribose) polymerase is enhanced in cells deficient in DNA double-strand break repair. Mol Cancer Ther (2010)9: 1775-1787.
47. Chalmers AJ, Lakshman M, Chan N and Bristow RG: Poly (ADP-ribose) polymerase inhibition as a model for synthetic lethality in developing radiation oncology targets. Semin Radiat Oncol (2010) 20: 274-281.
48. Camphausen K and Tofilon PJ: Inhibition of Hsp90: a multitarget approach to radiosensitization. Clin Cancer Res (2007) 13: 4326-4330.
49. Kabakov AE, Kudryavtsev VA and Gabai VL: Hsp90 inhibitors as promising agents for radiotherapy. J Mol Med (Berl) (2010) 88: 241-247.
50. Lapenna S and Giordano A: Cell cycle kinases as therapeutic tar gets for cancer. Nat Rev Drug Discov (2009) 8: 547-566.
51. Tofilon PJ and Camphausen K: Molecular targets for tumor radio sensitization. Chem Rev (2009) 109: 2974-2988.
52. Savitsky K, Bar-Shira A, Gilad S, Rotman G, Ziv Y, Vanagaite L, Tagle DA, Smith S, Uziel T, Sfez S, Ashkenazi M, Pecker I, Frydman M, Harnik R, Patanjali SR, Simmons A, Clines GA, Sartiel A, Gatti RA, Chessa L, Sanal O, Lavin MF, Jaspers NG, Taylor AM, Arlett CF, Miki T, Weissman SM, Lovett M, Collins FS and Shiloh Y: A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science (1995) 268: 1749-1753.
53. Shiloh Y: Ataxia-telangiectasia and the Nijmegen breakage syndrome: related disorders but genes apart. Annu Rev Genet (1997)31: 635-662.
54. Eriksson D and Stigbrand T: Radiation-induced cell death mecha nisms. Tumour Biol (2010) 31: 363-372.
55. Postiglione I, Chiaviello A and Palumbo G: Twilight effects of low doses of ionizing radiation on cellular systems: a bird's eye view on current concepts and research. Med Oncol (2010) 27: 495-509.
56. Riesterer O, Matsumoto F, Wang L, Pickett J, Molkentine D, Giri U, Milas L and Raju U: A novel Chk inhibitor, XL-844, increases human cancer cell radiosensitivity through promotion of mitotic catastrophe. Invest New Drugs (2011) 29: 514-522.
57. Morgan MA, Parsels LA, Zhao L, Parsels JD, Davis MA, Hassan MC, Arumugarajah S, Hylander-Gans L, Morosini D, Simeone DM, Canman CE, Normolle DP, Zabludoff SD, Maybaum J and Lawrence TS: 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.
58. Shrivastav M, De Haro LP and Nickoloff JA: Regulation of DNA double-strand break repair pathway choice. Cell Res (2008) 18: 134-147.
59. Alao JP and Sunnerhagen P: The ATM and ATR inhibitors CGK733 and caffeine suppress cyclin D1 levels and inhibit cell proliferation. Radiat Oncol (2009) 4: 51.
60. Sarkaria JN, Tibbetts RS, Busby EC, Kennedy AP, Hill DE and Abraham RT: Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing agent wortmannin. Cancer Res (1998) 58: 4375-4382.
61. Zhou BB, Chaturvedi P, Spring K, Scott SP, Johanson RA, Mishra R, Mattern MR, Winkler JD and Khanna KK: Caffeine abolishes the mammalian G(2)/M DNA damage checkpoint by inhibiting ataxia-telangiectasia-mutated kinase activity. J Biol Chem (2000) 275: 10342-10348.
62. Hickson I, Zhao Y, Richardson CJ, Green SJ, Martin NM, Orr Al, Reaper PM, Jackson SP, Curtin NJ and Smith GC: Identification and characterization of a novel and specific inhibitor of the ataxiatelangiectasia mutated kinase ATM. Cancer Res (2004) 64: 9152 9159.
63. Won J, Kim M, Kim N, Ahn JH, Lee WG, Kim SS, Chang KY, Yi YW and Kim TK: Small molecule-based reversible reprogramming of cellular lifespan. Nat Chem Biol (2006) 2: 369-374.
64. Rainey MD, Charlton ME, Stanton RV and Kastan MB: Transient inhibition of ATM kinase is sufficient to enhance cellular sensitivity to ionizing radiation. Cancer Res (2008) 68: 7466-7474.
65. Collis SJ, Swartz MJ, Nelson WG and DeWeese TL: Enhanced radiation and chemotherapy-mediated cell killing of human cancer cells by small inhibitory RNA silencing of DNA repair factors. Cancer Res (2003) 63: 1550-1554.
66. Guha C, Guha U, Tribius S, Alfieri A, Casper D, Chakravarty P, Mellado W, Pandita TK and Vikram B: Antisense ATM gene therapy: a strategy to increase the radiosensitivity of human tumors. Gene Ther (2000) 7: 852-858.
67. Ajimura M, Leem SH and Ogawa H: Identification of new genes required for meiotic recombination in Saccharomyces cerevisiae. Genetics (1993) 133: 51-66.
68. Parry JM, Davies PJ and Evans WE: The effects of "cell age" upon the lethal effects of physical and chemical mutagens in the yeast, Saccharomyces cerevisiae. Mol Gen Genet (1976) 146: 27-35.
69. Carney JP, Maser RS, Olivares H, Davis EM, Le Beau M, Yates JR, 3rd, Hays L, Morgan WF and Petrini JH: The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell (1998)93: 477-486.
70. Stewart GS, Maser RS, Stankovic T, Bressan DA, Kaplan Ml, Jaspers NG, Raams A, Byrd PJ, Petrini JH and Taylor AM: The DNA double-strand break repair gene hMRE11 is mutated in indi viduals with an ataxia-telangiectasia-like disorder. Cell (1999) 99: 577-587.
71. Waltes R, Kalb R, Gatei M, Kijas AW, Stumm M, Sobeck A, Wieland B, Varon R, Lerenthal Y, Lavin MF, Schindler D and Dork T:Human RAD50 deficiency in a Nijmegen breakage syn drome-like disorder. Am J Hum Genet (2009) 84: 605-616.
72. Williams RS, Williams JS and Tainer JA: Mre11-Rad50-Nbs1 is a keystone complex connecting DNA repair machinery, doublestrand break signaling, and the chromatin template. Biochem Cell Biol (2007)85: 509-520.
73. Nelms BE, Maser RS, MacKayJF, Lagally MG and Petrini JH: In situ visualization of DNA double-strand break repair in human fibroblasts. Science (1998) 280: 590-592.
74. Paull TT: Making the best of the loose ends: Mre11/Rad50 com plexes and Sae2 promote DNA double-strand break resection. DNA Repair (Amst) (2010) 9: 1283-1291.
75. Di Virgilio M and Gautier J: Repair of double-strand breaks by nonhomologous end joining in the absence of Mre11. J Cell Biol (2005) 171: 765-771.
76. Dupre A, Boyer-Chatenet L, Sattler RM, Modi AP, Lee JH, Nicolette ML, Kopelovich L, Jasin M, Baer R, Paull TT and Gautier J: A forward chemical genetic screen reveals an inhibitor of the Mre11-Rad50-Nbs1 complex. Nat Chem Biol (2008) 4: 119-125.
77. Garner KM, Pletnev AA and Eastman A: Corrected structure of mirin, a small-molecule inhibitor of the Mre11-Rad50-Nbs1 com plex. Nat Chem Biol (2009) 5: 129-130; author reply 130.
78. Kuroda S, Fujiwara T, Shirakawa Y, Yamasaki Y, Yano S, Uno F, Tazawa H, Hashimoto Y, Watanabe Y, Noma K, Urata Y and Kagawa S: Telomerase-dependent oncolytic adenovirus sensitizes human cancer cells to ionizing radiation via inhibition of DNA repair machinery. Cancer Res (2010) 70: 9339-9348.
79. Kawashima T, Kagawa S, Kobayashi N, Shirakiya Y, Umeoka T, Teraishi F, Taki M, Kyo S, Tanaka N and Fujiwara T: Telomerase-specific replication-selective virotherapy for human cancer. Clin Cancer Res (2004) 10: 285-292.
80. Umeoka T, Kawashima T, Kagawa S, Teraishi F, Taki M, Nishizaki M, Kyo S, Nagai K, Urata Y, Tanaka N and Fujiwara T: Visualization of intrathoracically disseminated solid tumors in mice with optical imaging by telomerase-specific amplification of a transferred green fluorescent protein gene. Cancer Res (2004) 64: 6259-6265.
81. Hashimoto Y, Watanabe Y, Shirakiya Y, Uno F, Kagawa S, Kawamura H, Nagai K, Tanaka N, Kumon H, Urata Y and Fujiwara T: Establishment of biological and pharmacokinetic assays of telomerase-specific replication-selective adenovirus. Cancer Sci (2008) 99: 385-390.
82. Nemunaitis J, Tong AW, Nemunaitis M, Senzer N, Phadke AP, Bedell C, Adams N, Zhang YA, Maples PB, Chen S, Pappen B, Burke J, Ichimaru D, Urata Y and Fujiwara T: A phase I study of telomerase-specific replication competent oncolytic adenovirus (telomelysin) for various solid tumors. Mol Ther (2010) 18: 429-434.
83. Blackford AN and Grand RJ: Adenovirus E1B 55-kilodalton protein: multiple roles in viral infection and cell transformation. J Virol (2009) 83: 4000-4012.
84. Stracker TH, Carson CT and Weitzman MD: Adenovirus oncoproteins inactivate the Mre11-Rad50-NBS1 DNA repair complex. Nature (2002) 418: 348-352.
85. Carson CT, Schwartz RA, Stracker TH, Lilley CE, Lee DV and Weitzman MD: The Mre11 complex is required for ATM activation and the G2/M checkpoint. EMBO J (2003) 22: 6610-6620.
86. Schwartz RA, Lakdawala SS, Eshleman HD, Russell MR, Carson CT and Weitzman MD: Distinct requirements of adenovirus E1b55K protein for degradation of cellular substrates. J Virol (2008) 82: 9043-9055.
87. Bischoff JR, Kirn DH, Williams A, Heise C, Horn S, Muna M, Ng L, NyeJA, Sampson-Johannes A, Fattaey A and McCormick F: An adenovirus mutant that replicates selectively in p53-deficient human tumor cells. Science (1996) 274: 373-376.
88. Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R and Langer R: Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol (2007)2: 751-760.
89. Majumdar D, Peng XH and Shin DM: The medicinal chemistry of theragnostics, multimodality imaging and applications of nanotechnology in cancer. Curr Top Med Chem (2010) 10: 1211-1226.
90. Eto Y, Yoshioka Y, Mukai Y, Okada N and Nakagawa S: Development of PEGylated adenovirus vector with targeting ligand. Int J Pharm (2008)354: 3-8