Targeting DNA repair, DNA metabolism and replication stress as anti-cancer strategies

FEBS Journal

Volumn 283, Issue 2, 2016, Pages 232-245

  Puigvert, Jordi Carreras ^a   Sanjiv, Kumar ^a   Helleday, Thomas ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

Author keywords

anti cancer therapy; DNA damage; DNA metabolism; oncogenic stress; replication stress

Indexed keywords

ANTINEOPLASTIC AGENT; ANTINEOPLASTIC ANTIMETABOLITE; CELL DNA; CHECKPOINT KINASE 1 INHIBITOR; CHECKPOINT KINASE INHIBITOR; CHLORMETHINE; CYCLIN DEPENDENT KINASE INHIBITOR; MTH1 INHIBITOR; PLATINUM COMPLEX; UNCLASSIFIED DRUG; WEE1 INHIBITOR; 8-OXODGTPASE; ATM PROTEIN; ATR PROTEIN, HUMAN; DNA LIGASE; PHOSPHATASE;

CANCER CELL; CANCER CHEMOTHERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER GENETICS; CANCER MORTALITY; CELL STRESS; DNA METABOLISM; DNA REPAIR; DNA REPLICATION; DOUBLE STRANDED DNA BREAK; DRUG SAFETY; DRUG TARGETING; GENE ACTIVATION; GENE ACTIVITY; GENE TARGETING; GENOTYPE; HUMAN; MALIGNANT NEOPLASTIC DISEASE; NONHUMAN; ONCOGENE; OXIDATIVE STRESS; PHENOTYPE; PRIORITY JOURNAL; REVIEW; RNA PROCESSING; ANTAGONISTS AND INHIBITORS; DRUG EFFECTS; GENETICS; MOLECULARLY TARGETED THERAPY; NEOPLASMS; PATHOLOGY; PROCEDURES;

ANTINEOPLASTIC AGENTS; ATAXIA TELANGIECTASIA MUTATED PROTEINS; DNA REPAIR; DNA REPAIR ENZYMES; DNA REPLICATION; HUMANS; MOLECULAR TARGETED THERAPY; NEOPLASMS; PHOSPHORIC MONOESTER HYDROLASES;

EID: 84957541686     PISSN: 1742464X     EISSN: 17424658     Source Type: Journal    
DOI: 10.1111/febs.13574     Document Type: Review

References (115)

1. Burrell RA, McGranahan N, Bartek J, &, Swanton C, (2013) The causes and consequences of genetic heterogeneity in cancer evolution. Nature 501, 338-345.
2. Hanahan D, &, Weinberg RA, (2011) Hallmarks of cancer: the next generation. Cell 144, 646-674.
3. Collins AR, (1999) Oxidative DNA damage, antioxidants, and cancer. BioEssays 21, 238-246.
4. Lindahl T, (1993) Instability and decay of the primary structure of DNA. Nature 362, 709-715.
5. Hoeijmakers JH, (2001) Genome maintenance mechanisms for preventing cancer. Nature 411, 366-374.
6. Remus D, &, Diffley JF, (2009) Eukaryotic DNA replication control: lock and load, then fire. Curr Opin Cell Biol 21, 771-777.
7. Gaillard H, Herrera-Moyano E, &, Aguilera A, (2013) Transcription-associated genome instability. Chem Rev 113, 8638-8661.
8. Mortusewicz O, Schermelleh L, Walter J, Cardoso MC, &, Leonhardt H, (2005) Recruitment of DNA methyltransferase I to DNA repair sites. Proc Natl Acad Sci USA 102, 8905-8909.
9. Bianchi V, Pontis E, &, Reichard P, (1986) Changes of deoxyribonucleoside triphosphate pools induced by hydroxyurea and their relation to DNA synthesis. J Biol Chem 261, 16037-16042.
10. Cerqueira NM, Fernandes PA, &, Ramos MJ, (2007) Understanding ribonucleotide reductase inactivation by gemcitabine. Chemistry 13, 8507-8515.
11. Petermann E, Woodcock M, &, Helleday T, (2010) Chk1 promotes replication fork progression by controlling replication initiation. Proc Natl Acad Sci USA 107, 16090-16095.
12. Jones RM, Mortusewicz O, Afzal I, Lorvellec M, Garcia P, Helleday T, &, Petermann E, (2013) Increased replication initiation and conflicts with transcription underlie Cyclin E-induced replication stress. Oncogene 32, 3744-3753.
13. Bartkova J, Rezaei N, Liontos M, Karakaidos P, Kletsas D, Issaeva N, Vassiliou LV, Kolettas E, Niforou K, Zoumpourlis VC, et al,. (2006) Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 444, 633-637.
14. Azvolinsky A, Giresi PG, Lieb JD, &, Zakian VA, (2009) Highly transcribed RNA polymerase II genes are impediments to replication fork progression in Saccharomyces cerevisiae. Mol Cell 34, 722-734.
15. Sale JE, Lehmann AR, &, Woodgate R, (2012) Y-family DNA polymerases and their role in tolerance of cellular DNA damage. Nat Rev Mol Cell Biol 13, 141-152.
16. Groth P, Auslander S, Majumder MM, Schultz N, Johansson F, Petermann E, &, Helleday T, (2010) Methylated DNA causes a physical block to replication forks independently of damage signalling, O(6)-methylguanine or DNA single-strand breaks and results in DNA damage. J Mol Biol 402, 70-82.
17. Merrick CJ, Jackson D, &, Diffley JF, (2004) Visualization of altered replication dynamics after DNA damage in human cells. J Biol Chem 279, 20067-20075.
18. Cheung-Ong K, Giaever G, &, Nislow C, (2013) DNA-damaging agents in cancer chemotherapy: serendipity and chemical biology. Chem Biol 20, 648-659.
19. Siddik ZH, (2003) Cisplatin: mode of cytotoxic action and molecular basis of resistance. Oncogene 22, 7265-7279.
20. Zhang J, Stevens MF, &, Bradshaw TD, (2012) Temozolomide: mechanisms of action, repair and resistance. Curr Mol Pharmacol 5, 102-114.
21. Curtin NJ, (2012) DNA repair dysregulation from cancer driver to therapeutic target. Nat Rev Cancer 12, 801-817.
22. Helleday T, Petermann E, Lundin C, Hodgson B, &, Sharma RA, (2008) DNA repair pathways as targets for cancer therapy. Nat Rev Cancer 8, 193-204.
23. Gad H, Koolmeister T, Jemth AS, Eshtad S, Jacques SA, Strom CE, Svensson LM, Schultz N, Lundback T, Einarsdottir BO, et al,. (2014) MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool. Nature 508, 215-221.
24. Murga M, Campaner S, Lopez-Contreras AJ, Toledo LI, Soria R, Montana MF, D'Artista L, Schleker T, Guerra C, Garcia E, et al,. (2011) Exploiting oncogene-induced replicative stress for the selective killing of Myc-driven tumors. Nat Struct Mol Biol 18, 1331-1335.
25. Huber KV, Salah E, Radic B, Gridling M, Elkins JM, Stukalov A, Jemth AS, Gokturk C, Sanjiv K, Stromberg K, et al,. (2014) Stereospecific targeting of MTH1 by (S)-crizotinib as an anticancer strategy. Nature 508, 222-227.
26. Casorelli I, Russo MT, &, Bignami M, (2008) Role of mismatch repair and MGMT in response to anticancer therapies. Anticancer Agents Med Chem 8, 368-380.
27. Liu L, &, Gerson SL, (2006) Targeted modulation of MGMT: clinical implications. Clin Cancer Res 12, 328-331.
28. Fortini P, &, Dogliotti E, (2010) Mechanisms of dealing with DNA damage in terminally differentiated cells. Mutat Res 685, 38-44.
29. Sweasy JB, Lang T, &, DiMaio D, (2006) Is base excision repair a tumor suppressor mechanism? Cell Cycle 5, 250-259.
30. Abbotts R, &, Madhusudan S, (2010) Human AP endonuclease 1 (APE1): from mechanistic insights to druggable target in cancer. Cancer Treat Rev 36, 425-435.
31. Naegeli H, &, Sugasawa K, (2011) The xeroderma pigmentosum pathway: decision tree analysis of DNA quality. DNA Repair (Amst) 10, 673-683.
32. Andressoo JO, Hoeijmakers JH, &, de Waard H, (2005) Nucleotide excision repair and its connection with cancer and ageing. Adv Exp Med Biol 570, 45-83.
33. Guo C, Kosarek-Stancel JN, Tang TS, &, Friedberg EC, (2009) Y-family DNA polymerases in mammalian cells. Cell Mol Life Sci 66, 2363-2381.
34. Lange SS, Takata K, &, Wood RD, (2011) DNA polymerases and cancer. Nat Rev Cancer 11, 96-110.
35. Kunkel TA, &, Erie DA, (2005) DNA mismatch repair. Annu Rev Biochem 74, 681-710.
36. Karran P, &, Bignami M, (1994) DNA damage tolerance, mismatch repair and genome instability. BioEssays 16, 833-839.
37. Wang W, (2007) Emergence of a DNA-damage response network consisting of Fanconi anaemia and BRCA proteins. Nat Rev Genet 8, 735-748.
38. Bogliolo M, &, Surralles J, (2015) Fanconi anemia: a model disease for studies on human genetics and advanced therapeutics. Curr Opin Genet Dev 33, 32-40.
39. Segui N, Mina LB, Lazaro C, Sanz-Pamplona R, Pons T, Navarro M, Bellido F, Lopez-Doriga A, Valdes-Mas R, Pineda M, et al,. (2015) Germline mutations in FAN1 cause hereditary colorectal cancer by impairing DNA repair. Gastroenterology 149, 563-566.
40. Shrivastav M, De Haro LP, &, Nickoloff JA, (2008) Regulation of DNA double-strand break repair pathway choice. Cell Res 18, 134-147.
41. Willems P, Claes K, Baeyens A, Vandersickel V, Werbrouck J, De Ruyck K, Poppe B, Van den Broecke R, Makar A, Marras E, et al,. (2008) Polymorphisms in nonhomologous end-joining genes associated with breast cancer risk and chromosomal radiosensitivity. Genes Chromosom Cancer 47, 137-148.
42. Esteller M, Silva JM, Dominguez G, Bonilla F, Matias-Guiu X, Lerma E, Bussaglia E, Prat J, Harkes IC, Repasky EA, et al,. (2000) Promoter hypermethylation and BRCA1 inactivation in sporadic breast and ovarian tumors. J Natl Cancer Inst 92, 564-569.
43. Rosenberg PS, Greene MH, &, Alter BP, (2003) Cancer incidence in persons with Fanconi anemia. Blood 101, 822-826.
44. Larminat F, Germanier M, Papouli E, &, Defais M, (2002) Deficiency in BRCA2 leads to increase in non-conservative homologous recombination. Oncogene 21, 5188-5192.
45. Mehta A, &, Haber JE, (2014) Sources of DNA double-strand breaks and models of recombinational DNA repair. Cold Spring Harb Perspect Biol 6, a016428.
46. Kolas NK, Chapman JR, Nakada S, Ylanko J, Chahwan R, Sweeney FD, Panier S, Mendez M, Wildenhain J, Thomson TM, et al,. (2007) Orchestration of the DNA-damage response by the RNF8 ubiquitin ligase. Science 318, 1637-1640.
47. Paulsen RD, Soni DV, Wollman R, Hahn AT, Yee MC, Guan A, Hesley JA, Miller SC, Cromwell EF, Solow-Cordero DE, et al,. (2009) A genome-wide siRNA screen reveals diverse cellular processes and pathways that mediate genome stability. Mol Cell 35, 228-239.
48. Carreras Puigvert J, von Stechow L, Siddappa R, Pines A, Bahjat M, Haazen LC, Olsen JV, Vrieling H, Meerman JH, Mullenders LH, et al,. (2013) Systems biology approach identifies the kinase Csnk1a1 as a regulator of the DNA damage response in embryonic stem cells. Sci Signal 6, ra5.
49. Chirnomas D, Taniguchi T, de la Vega M, Vaidya AP, Vasserman M, Hartman AR, Kennedy R, Foster R, Mahoney J, Seiden MV, et al,. (2006) Chemosensitization to cisplatin by inhibitors of the Fanconi anemia/BRCA pathway. Mol Cancer Ther 5, 952-961.
50. Bin Z, Xiubin G, Uppalapati U, Ashwell MA, Leggett DS, &, Li CJ, (2008) High-content fluorescent-based assay for screening activators of DNA damage checkpoint pathways. J Biomol Screen 13, 538-543.
51. Davies KD, Cable PL, Garrus JE, Sullivan FX, von Carlowitz I, Huerou YL, Wallace E, Woessner RD, &, Gross S, (2011) Chk1 inhibition and Wee1 inhibition combine synergistically to impede cellular proliferation. Cancer Biol Ther 12, 788-796.
52. Goglia AG, Delsite R, Luz AN, Shahbazian D, Salem AF, Sundaram RK, Chiaravalli J, Hendrikx PJ, Wilshire JA, Jasin M, et al,. (2015) Identification of novel radiosensitizers in a high-throughput, cell-based screen for DSB repair inhibitors. Mol Cancer Ther 14, 326-342.
53. FitzGerald J, Murillo LS, O'Brien G, O'Connell E, O'Connor A, Wu K, Wang GN, Rainey MD, Natoni A, Healy S, et al,. (2014) A high through-put screen for small molecules modulating MCM2 phosphorylation identifies Ryuvidine as an inducer of the DNA damage response. PLoS One 9, e98891.
54. Alekseev S, Ayadi M, Brino L, Egly JM, Larsen AK, &, Coin F, (2014) A small molecule screen identifies an inhibitor of DNA repair inducing the degradation of TFIIH and the chemosensitization of tumor cells to platinum. Chem Biol 21, 398-407.
55. Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, et al,. (2005) Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434, 917-921.
56. Pearl LH, Schierz AC, Ward SE, Al-Lazikani B, &, Pearl FM, (2015) Therapeutic opportunities within the DNA damage response. Nat Rev Cancer 15, 166-180.
57. Gorgoulis VG, Vassiliou LV, Karakaidos P, Zacharatos P, Kotsinas A, Liloglou T, Venere M, Ditullio RA Jr, Kastrinakis NG, Levy B, et al,. (2005) Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature 434, 907-913.
58. Halazonetis TD, Gorgoulis VG, &, Bartek J, (2008) An oncogene-induced DNA damage model for cancer development. Science 319, 1352-1355.
59. Arnaudeau C, Lundin C, &, Helleday T, (2001) DNA double-strand breaks associated with replication forks are predominantly repaired by homologous recombination involving an exchange mechanism in mammalian cells. J Mol Biol 307, 1235-1245.
60. Lundin C, Erixon K, Arnaudeau C, Schultz N, Jenssen D, Meuth M, &, Helleday T, (2002) Different roles for nonhomologous end joining and homologous recombination following replication arrest in mammalian cells. Mol Cell Biol 22, 5869-5878.
61. Casper AM, Nghiem P, Arlt MF, &, Glover TW, (2002) ATR regulates fragile site stability. Cell 111, 779-789.
62. Tsantoulis PK, Kotsinas A, Sfikakis PP, Evangelou K, Sideridou M, Levy B, Mo L, Kittas C, Wu XR, Papavassiliou AG, et al,. (2008) Oncogene-induced replication stress preferentially targets common fragile sites in preneoplastic lesions. A genome-wide study. Oncogene 27, 3256-3264.
63. Barlow JH, Faryabi RB, Callen E, Wong N, Malhowski A, Chen HT, Gutierrez-Cruz G, Sun HW, McKinnon P, Wright G, et al,. (2013) Identification of early replicating fragile sites that contribute to genome instability. Cell 152, 620-632.
64. Suram A, Kaplunov J, Patel PL, Ruan H, Cerutti A, Boccardi V, Fumagalli M, Di Micco R, Mirani N, Gurung RL, et al,. (2012) Oncogene-induced telomere dysfunction enforces cellular senescence in human cancer precursor lesions. EMBO J 31, 2839-2851.
65. Rooney S, Alt FW, Lombard D, Whitlow S, Eckersdorff M, Fleming J, Fugmann S, Ferguson DO, Schatz DG, &, Sekiguchi J, (2003) Defective DNA repair and increased genomic instability in Artemis-deficient murine cells. J Exp Med 197, 553-565.
66. Plug-DeMaggio AW, Sundsvold T, Wurscher MA, Koop JI, Klingelhutz AJ, &, McDougall JK, (2004) Telomere erosion and chromosomal instability in cells expressing the HPV oncogene 16E6. Oncogene 23, 3561-3571.
67. Burrell RA, McClelland SE, Endesfelder D, Groth P, Weller MC, Shaikh N, Domingo E, Kanu N, Dewhurst SM, Gronroos E, et al,. (2013) Replication stress links structural and numerical cancer chromosomal instability. Nature 494, 492-496.
68. Bester AC, Roniger M, Oren YS, Im MM, Sarni D, Chaoat M, Bensimon A, Zamir G, Shewach DS, &, Kerem B, (2011) Nucleotide deficiency promotes genomic instability in early stages of cancer development. Cell 145, 435-446.
69. Gottipati P, Cassel TN, Savolainen L, &, Helleday T, (2008) Transcription-associated recombination is dependent on replication in Mammalian cells. Mol Cell Biol 28, 154-164.
70. Alzu A, Bermejo R, Begnis M, Lucca C, Piccini D, Carotenuto W, Saponaro M, Brambati A, Cocito A, Foiani M, et al,. (2012) Senataxin associates with replication forks to protect fork integrity across RNA-polymerase-II-transcribed genes. Cell 151, 835-846.
71. Petermann E, Orta ML, Issaeva N, Schultz N, &, Helleday T, (2010) Hydroxyurea-stalled replication forks become progressively inactivated and require two different RAD51-mediated pathways for restart and repair. Mol Cell 37, 492-502.
72. Toledo LI, Altmeyer M, Rask MB, Lukas C, Larsen DH, Povlsen LK, Bekker-Jensen S, Mailand N, Bartek J, &, Lukas J, (2013) ATR prohibits replication catastrophe by preventing global exhaustion of RPA. Cell 155, 1088-1103.
73. Aguilera A, (2002) The connection between transcription and genomic instability. EMBO J 21, 195-201.
74. Toledo LI, Murga M, Zur R, Soria R, Rodriguez A, Martinez S, Oyarzabal J, Pastor J, Bischoff JR, &, Fernandez-Capetillo O, (2011) A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations. Nat Struct Mol Biol 18, 721-727.
75. Hekmat-Nejad M, You Z, Yee MC, Newport JW, &, Cimprich KA, (2000) Xenopus ATR is a replication-dependent chromatin-binding protein required for the DNA replication checkpoint. Curr Biol 10, 1565-1573.
76. Cimprich KA, &, Cortez D, (2008) ATR: an essential regulator of genome integrity. Nat Rev Mol Cell Biol 9, 616-627.
77. Hoglund A, Nilsson LM, Muralidharan SV, Hasvold LA, Merta P, Rudelius M, Nikolova V, Keller U, &, Nilsson JA, (2011) Therapeutic implications for the induced levels of Chk1 in Myc-expressing cancer cells. Clin Cancer Res 17, 7067-7079.
78. Toledo LI, Murga M, &, Fernandez-Capetillo O, (2011) Targeting ATR and Chk1 kinases for cancer treatment: a new model for new (and old) drugs. Mol Oncol 5, 368-373.
79. Reaper PM, Griffiths MR, Long JM, Charrier JD, Maccormick S, Charlton PA, Golec JM, &, Pollard JR, (2011) Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR. Nat Chem Biol 7, 428-430.
80. Rothkamm K, &, Lobrich M, (2003) Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses. Proc Natl Acad Sci USA 100, 5057-5062.
81. Zabludoff SD, Deng C, Grondine MR, Sheehy AM, Ashwell S, Caleb BL, Green S, Haye HR, Horn CL, Janetka JW, et al,. (2008) AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies. Mol Cancer Ther 7, 2955-2966.
82. Cliby WA, Roberts CJ, Cimprich KA, Stringer CM, Lamb JR, Schreiber SL, &, Friend SH, (1998) Overexpression of a kinase-inactive ATR protein causes sensitivity to DNA-damaging agents and defects in cell cycle checkpoints. EMBO J 17, 159-169.
83. Wilsker D, Petermann E, Helleday T, &, Bunz F, (2008) Essential function of Chk1 can be uncoupled from DNA damage checkpoint and replication control. Proc Natl Acad Sci USA 105, 20752-20757.
84. Foote KM, Lau A, &, Nissink JW, (2015) Drugging ATR: progress in the development of specific inhibitors for the treatment of cancer. Future Med Chem 7, 873-891.
85. Huntoon CJ, Flatten KS, Wahner Hendrickson AE, Huehls AM, Sutor SL, Kaufmann SH, &, Karnitz LM, (2013) ATR inhibition broadly sensitizes ovarian cancer cells to chemotherapy independent of BRCA status. Cancer Res 73, 3683-3691.
86. Josse R, Martin SE, Guha R, Ormanoglu P, Pfister TD, Reaper PM, Barnes CS, Jones J, Charlton P, Pollard JR, et al,. (2014) ATR inhibitors VE-821 and VX-970 sensitize cancer cells to topoisomerase i inhibitors by disabling DNA replication initiation and fork elongation responses. Cancer Res 74, 6968-6979.
87. Fokas E, Prevo R, Pollard JR, Reaper PM, Charlton PA, Cornelissen B, Vallis KA, Hammond EM, Olcina MM, Gillies McKenna W, et al,. (2012) Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation. Cell Death Dis 3, e441.
88. Ma CX, Janetka JW, &, Piwnica-Worms H, (2011) Death by releasing the breaks: CHK1 inhibitors as cancer therapeutics. Trends Mol Med 17, 88-96.
89. Ma CX, Ellis MJ, Petroni GR, Guo Z, Cai SR, Ryan CE, Craig Lockhart A, Naughton MJ, Pluard TJ, Brenin CM, et al,. (2013) A phase II study of UCN-01 in combination with irinotecan in patients with metastatic triple negative breast cancer. Breast Cancer Res Treat 137, 483-492.
90. Aarts M, Sharpe R, Garcia-Murillas I, Gevensleben H, Hurd MS, Shumway SD, Toniatti C, Ashworth A, &, Turner NC, (2012) Forced mitotic entry of S-phase cells as a therapeutic strategy induced by inhibition of WEE1. Cancer Discov 2, 524-539.
91. Do K, Doroshow JH, &, Kummar S, (2013) Wee1 kinase as a target for cancer therapy. Cell Cycle 12, 3159-3164.
92. VanArsdale T, Boshoff C, Arndt KT, &, Abraham RT, (2015) Molecular Pathways: targeting the Cyclin D-CDK4/6 Axis for Cancer Treatment. Clin Cancer Res 21, 2905-2910.
93. Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, et al,. (2013) Mutational landscape and significance across 12 major cancer types. Nature 502, 333-339.
94. Sholl LM, Aisner DL, Varella-Garcia M, Berry LD, Dias-Santagata D, Wistuba II, Chen H, Fujimoto J, Kugler K, Franklin WA, et al,. (2015) Multi-institutional Oncogenic Driver Mutation Analysis in Lung Adenocarcinoma: the Lung Cancer Mutation Consortium Experience. J Thorac Oncol 10, 768-777.
95. Helleday T, (2014) Cancer phenotypic lethality, exemplified by the non-essential MTH1 enzyme being required for cancer survival. Ann Oncol 25, 1253-1255.
96. Sakumi K, Furuichi M, Tsuzuki T, Kakuma T, Kawabata S, Maki H, &, Sekiguchi M, (1993) Cloning and expression of cDNA for a human enzyme that hydrolyzes 8-oxo-dGTP, a mutagenic substrate for DNA synthesis. J Biol Chem 268, 23524-23530.
97. Okamoto K, Toyokuni S, Kim WJ, Ogawa O, Kakehi Y, Arao S, Hiai H, &, Yoshida O, (1996) Overexpression of human mutT homologue gene messenger RNA in renal-cell carcinoma: evidence of persistent oxidative stress in cancer. Int J Cancer 65, 437-441.
98. Speina E, Arczewska KD, Gackowski D, Zielinska M, Siomek A, Kowalewski J, Olinski R, Tudek B, &, Kusmierek JT, (2005) Contribution of hMTH1 to the maintenance of 8-oxoguanine levels in lung DNA of non-small-cell lung cancer patients. J Natl Cancer Inst 97, 384-395.
99. Svensson LM, Jemth AS, Desroses M, Loseva O, Helleday T, Hogbom M, &, Stenmark P, (2011) Crystal structure of human MTH1 and the 8-oxo-dGMP product complex. FEBS Lett 585, 2617-2621.
100. Klaunig JE, Wang Z, Pu X, &, Zhou S, (2011) Oxidative stress and oxidative damage in chemical carcinogenesis. Toxicol Appl Pharmacol 254, 86-99.
101. Sosa V, Moline T, Somoza R, Paciucci R, Kondoh H, &, LLeonart ME, (2013) Oxidative stress and cancer: an overview. Ageing Res Rev 12, 376-390.
102. Gorrini C, Harris IS, &, Mak TW, (2013) Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov 12, 931-947.
103. Coskun E, Jaruga P, Jemth AS, Loseva O, Scanlan LD, Tona A, Lowenthal MS, Helleday T, &, Dizdaroglu M, (2015) Addiction to MTH1 protein results in intense expression in human breast cancer tissue as measured by liquid chromatography-isotope-dilution tandem mass spectrometry. DNA Repair (Amst) 33, 101-110.
104. Giribaldi MG, Munoz A, Halvorsen K, Patel A, &, Rai P, (2015) MTH1 expression is required for effective transformation by oncogenic HRAS. Oncotarget 6, 11519-11529.
105. Patel A, Burton DG, Halvorsen K, Balkan W, Reiner T, Perez-Stable C, Cohen A, Munoz A, Giribaldi MG, Singh S, et al,. (2015) MutT Homolog 1 (MTH1) maintains multiple KRAS-driven pro-malignant pathways. Oncogene 34, 2586-2596.
106. Cai JP, Ishibashi T, Takagi Y, Hayakawa H, &, Sekiguchi M, (2003) Mouse MTH2 protein which prevents mutations caused by 8-oxoguanine nucleotides. Biochem Biophys Res Commun 305, 1073-1077.
107. Takagi Y, Setoyama D, Ito R, Kamiya H, Yamagata Y, &, Sekiguchi M, (2012) Human MTH3 (NUDT18) protein hydrolyzes oxidized forms of guanosine and deoxyguanosine diphosphates: comparison with MTH1 and MTH2. J Biol Chem 287, 21541-21549.
108. Carter M, Jemth AS, Hagenkort A, Page BD, Gustafsson R, Griese JJ, Gad H, Valerie NC, Desroses M, Bostrom J, et al,. (2015) Crystal structure, biochemical and cellular activities demonstrate separate functions of MTH1 and MTH2. Nat Commun 6, 7871.
109. Chaudhuri L, Vincelette ND, Koh BD, Naylor RM, Flatten KS, Peterson KL, McNally A, Gojo I, Karp JE, Mesa RA, et al,. (2014) CHK1 and WEE1 inhibition combine synergistically to enhance therapeutic efficacy in acute myeloid leukemia ex vivo. Haematologica 99, 688-696.
110. Gerlinger M, Rowan AJ, Horswell S, Larkin J, Endesfelder D, Gronroos E, Martinez P, Matthews N, Stewart A, Tarpey P, et al,. (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 366, 883-892.
111. Morales C, Ribas M, Aiza G, &, Peinado MA, (2005) Genetic determinants of methotrexate responsiveness and resistance in colon cancer cells. Oncogene 24, 6842-6847.
112. Galluzzi L, Senovilla L, Vitale I, Michels J, Martins I, Kepp O, Castedo M, &, Kroemer G, (2012) Molecular mechanisms of cisplatin resistance. Oncogene 31, 1869-1883.
113. Shalem O, Sanjana NE, Hartenian E, Shi X, Scott DA, Mikkelsen TS, Heckl D, Ebert BL, Root DE, Doench JG, et al,. (2014) Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 343, 84-87.
114. Wang T, Wei JJ, Sabatini DM, &, Lander ES, (2014) Genetic screens in human cells using the CRISPR-Cas9 system. Science 343, 80-84.
115. Rodriguez R, &, Miller KM, (2014) Unravelling the genomic targets of small molecules using high-throughput sequencing. Nat Rev Genet 15, 783-796.