Chromatin-regulating proteins as targets for cancer therapy

Journal of Radiation Research

Volumn 55, Issue 4, 2014, Pages 613-628

  Oike, Takahiro ^a,b   Ogiwara, Hideaki ^a   Amornwichet, Napapat ^b,c   Nakano, Takashi ^b   Kohno, Takashi ^a  

^a NATIONAL CANCER CENTER RESEARCH INSTITUTE   (Japan)

^b GUNMA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^c CHULALONGKORN UNIVERSITY   (Thailand)

Author keywords

BRM; chromatin remodeling; histone acetyltransferase; histone modification; SWI SNF complex; synthetic lethality

Indexed keywords

ACETYLATION; CHEMOTHERAPY; CHROMOSOMES; DISEASES; ENCODING (SYMBOLS); IRRADIATION; MEDICAL APPLICATIONS; MOLECULES; ONCOLOGY; PROTEINS; SIGNAL ENCODING; TUMORS;

BRM; CANCER THERAPY; CHROMATIN REMODELLING; HISTONE ACETYLTRANSFERASES; HISTONE DEACETYLASES; HISTONE MODIFICATION; IONIZING IRRADIATION; SWI-SNF; SWI/SNF COMPLEX; SYNTHETIC LETHALITY;

RADIOTHERAPY;

CHROMATIN; HISTONE; HISTONE ACETYLTRANSFERASE; HISTONE DEACETYLASE INHIBITOR; RADIOSENSITIZING AGENT;

ANIMAL; ANTAGONISTS AND INHIBITORS; CHROMATIN; CHROMATIN ASSEMBLY AND DISASSEMBLY; GENETICS; HUMAN; METABOLISM; MOLECULARLY TARGETED THERAPY; MUTATION; NEOPLASMS; RADIOTHERAPY;

ANIMALS; CHROMATIN; CHROMATIN ASSEMBLY AND DISASSEMBLY; HISTONE ACETYLTRANSFERASES; HISTONE DEACETYLASE INHIBITORS; HISTONES; HUMANS; MOLECULAR TARGETED THERAPY; MUTATION; NEOPLASMS; RADIATION-SENSITIZING AGENTS; RADIOTHERAPY;

EID: 84905226604     PISSN: 04493060     EISSN: 13499157     Source Type: Journal    
DOI: 10.1093/jrr/rrt227     Document Type: Review

References (140)

1. Clapier CR, Cairns BR. The biology of chromatin remodeling complexes. Annu Rev Biochem 2009;78:273-304.
2. Rossetto D, Truman AW, Kron SJ et al. Epigenetic modifications in double-strand break DNA damage signaling and repair. Clin Cancer Res 2010;15:4543-52.
3. Carrozza MJ, Utley RT, Workman JL et al. The diverse functions of histone acetyltransferase complexes. Trends Genet 2003;19:321-9.
4. Ogiwara H, Ui A, Otsuka A et al. Histone acetylation by CBP and p300 at double-strand break sites facilitates SWI/SNF chromatin remodeling and the recruitment of non-homologous end joining factors. Oncogene 2011;5:2135-46.
5. Murr R, Loizou JI, Yang YG et al. Histone acetylation by Trrap-Tip60 modulates loading of repair proteins and repair of DNA double-strand breaks. Nat Cell Biol 2006;8:91-9.
6. Bird AW, Yu DY, Pray-Grant MG et al. Acetylation of histone H4 by Esa1 is required for DNA double-strand break repair. Nature 2002;419:411-5.
7. Ogiwara H, Kohno T. CBP and p300 histone acetyltrans-ferases contribute to homologous recombination by transcrip-tionally activating the BRCA1 and RAD51 genes. PLOS ONE 2012;7:e52810.
8. Balasubramanyam K, Varier RA, Altaf M et al. Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acet-yltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription. J Biol Chem 2004;279:51163-71.
9. Sun Y, Jiang X, Chen S et al. Inhibition of histone acetyl-transferase activity by anacardic acid sensitizes tumor cells to ionizing radiation. FEBS Lett 2006;580:4353-6.
10. Hemshekhar M, Sebastin SM, Kemparaju K et al. (21 November 2011) Emerging roles of anacardic acid and its derivatives: a pharmacological overview. Basic Clin Pharmacol Toxicol, 10.1111/j.1742-7843.2011.00833.x.
11. Balasubramanyam K, Swaminathan V, Ranganathan A et al. Small molecule modulators of histone acetyltransferase p300. J Biol Chem 2003;278:19134-40.
12. Balasubramanyam K, Altaf M, Varier RA et al. Polyisoprenylated benzphenone, garcinol, anatural histone acet-yltransferase inhibitor, represses chromatin transcription and alters global gene expression. J Biol Chem 2004;279:33716-26.
13. Oike T, Ogiwara H, Torikai K et al. Garcinol, a histone acet-yltransferase inhibitor, radiosensitizes cancer cells by inhibiting non-homologous end joining. Int J Radiat Oncol Biol Phys 2012;84:815-21.
14. Ogiwara H, Ui A, Shiotani B et al. Curcumin suppresses multiple DNA damage response pathways and has potency as a sensitizer to PARP inhibitor. Carcinogenesis 2013;34: 2486-97.
15. Khafif A, Lev-Ari S, Vexler A et al. Curcumin: a potential radio-enhancer in head and neck cancer. Laryngoscope 2009;119:2019-26.
16. Sandur SK, Deorukhkar A, Pandey MK et al. Curcumin modulates the radiosensitivity of colorectal cancer cells by suppressing constitutive and inducible NF-kB activity. Int J Radiat Oncol Biol Phys 2009;75:534-42.
17. Li M, Zhang Z, Hill DL et al. Curcumin, a dietary component, has anticancer, chemosensitization, and radiosensitization effects by down-regulating the MDM2 oncogene through the PI3K/mTOR/ETS2 pathway. Cancer Res 2007;67:1988-96.
18. Chendil D, Ranga RS, Meigooni D et al. Curcumin confers radiosensitizing effect in prostate cancer cell line PC-3. Oncogene 2004;23:1599-607.
19. Cate RT, Krawczwk P, Stap J et al. Radiosensitizing effect of the histone acetyltransferase inhibitor anacardic acid on various mammalian cell lines. Oncol Lett 2010;1:756-9.
20. Albert JM, Cao C, Kim KW et al. Inhibition of Poly (ADP-ribose) polymerase enhances cell death and improves tumor growth delay in irradiated lung cancer models. Clin Cancer Res 2007;13:3033-42.
21. Veuger SJ, Curtin NJ, Richardson CJ et al. 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;63:6008-15.
22. Dhandapani KM, Mahesh VB, Brann DW et al. Curcumin suppresses growth and chemoresistance of human glioblastoma cells via AP-1 and NFkappaB transcription factors. J Neurochem 2007;102:522-38.
23. Plummer SM, Holloway KA, Manson MM et al. Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopre-ventive agent curcumin involves inhibition of NF-kappaB activation via the NIK/IKK signalling complex. Oncogene 1999;18:6013-20.
24. Qiao Q, Jiang Y, Li G et al. Inhibition of the PI3K/AKT-NF-κB pathway with curcumin enhanced radiation-induced apoptosis in human Burkitt's lymphoma. J Pharmacol Sci 2013;121:247-56.
25. Padhye S, Ahmad A, Oswal N et al. Emerging role of Garcinol, the antioxidant chalcone from Garcinia indica Choisy and its synthetic analogs. J Hematol Oncol 2009;2:38.
26. Ahmad A, Wang Z, Ali R et al. Apoptosis-inducing effect of garcinol is mediated by NF-kappaB signaling in breast cancer cells. Cell Biochem 2010;109:1134-41.
27. Groselj B, Sharma NL, Hamdy FC et al. Histone deacetylase inhibitors as radiosensitisers: effects on DNA damage signalling and repair. Br J Cancer 2013;108:748-54.
28. Miller KM, Tjeertes JV, Coates J et al. Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining. Nat Struct Mol Biol 2010;17:1144-51.
29. Chinnaiyan P, Vallabhaneni G, Armstrong E et al. Modulation of radiation response by histone deacetylase inhibition. Int J Radiat Oncol Biol Phys 2005;62:223-9.
30. Chen X, Wong P, Radany EH et al. Suberoylanilide hydroxa-mic acid as a radiosensitizer through modulation of RAD51 protein and inhibition of homology-directed repair in multiple myeloma. Mol Cancer Res 2012;10:1052-64.
31. Blattmann C, Oertel S, Ehemann V et al. Enhancement of radiation response in osteosarcoma and rhabdomyosarcoma cell lines by histone deacetylase inhibition. Int J Radiat Oncol Biol Phys 2010;78:237-45.
32. Munshi A, Kurland J, Nishikawa T et al. Histone deacetylase inhibitors radiosensitize human melanoma cells by suppressing DNA repair activity. Clin Cancer Res 2005;11:4912-22.
33. Chen X, Wong P, Radany E et al. HDAC inhibitor, valproic acid, induces p53-dependent radiosensitization of colon cancer cells. Cancer Biother Radiopharm 2009;24:689-99.
34. Lan L, Ui A, Nakajima S et al. The ACF1 complex is required for DNA double-strand break repair in human cells. Mol Cell 2010;40:976-87.
35. Hall EJ, Giaccia AJ. Radiosensitizers and bioreductive drugs. In: McAllister L, Bierig L, Barret K (eds). Radiobiology for the Radiologist. Philadelphia: Lippincott Williams & Wilkins, 2006, 419-31.
36. Bolderson E, Richard DJ, Zhou BB et al. Recent advances in cancer therapy targeting proteins involved in DNA double-strand break repair. Clin Cancer Res 2009;15:6314-20.
37. Bucher N, Britten CD. G2 checkpoint abrogation and checkpoint kinase-1 targeting in the treatment of cancer. Br J Cancer 2008;98:523-8.
38. Oike T, Ogiwara H, Nakano T et al. Histone acetyltrans-ferases (HATs) involved in non-homologous end joining as a target for radiosensitization. In: Kataria T (ed). Frontiers in Radiation Oncology. Rijeka: Intech, 2013, 3-12.
39. Noguchi H, Yamashita H, Murakami T et al. Successful treatment of anaplastic thyroid carcinoma with a combination of oral valproic acid, chemotherapy, radiation and surgery. Endocr J 2009;56:245-9.
40. Masoudi A, Elopre M, Amini E et al. Influence of valproic acid on outcome of high-grade gliomas in children. Anticancer Res 2008;28:2437-42.
41. Ree AH, Dueland S, Folkvord S et al. Vorinostat, a histone deacetylase inhibitor, combined with pelvic palliative radiotherapy for gastrointestinal carcinoma: the pelvic radiation and vorinostat (PRAVO) phase 1 study. Lancet Oncol 2010;11:459-64.
42. Lorch Y, Maier-Davis B, Kornberg RD. Mechanism of chro-matin remodeling. Proc Natl Acad Sci USA 2010;107: 3458-62.
43. Saha A, Wittmeyer J, Cairns BR. Chromatin remodelling: the industrial revolution of DNA around histones. Nat Rev Mol Cell Biol 2006;7:437-47.
44. Medina PP, Carretero J, Ballestar E et al. Transcriptional targets of the chromatin-remodelling factor SMARCA4/BRG1 in lung cancer cells. Hum Mol Genet 2005;14: 973-82.
45. Trouche D, Le Chalony C, Muchardt C et al. RB and hbrm cooperate to repress the activation functions of E2F1. Proc Natl Acad Sci USA 1997;94:11268-73.
46. Isakoff MS, Sansam CG, Tamayo P et al. Inactivation of the Snf5 tumor suppressor stimulates cell cycle progression and cooperates with p53 loss in oncogenic transformation. Proc Natl Acad Sci USA 2005;102:17745-50.
47. Cheng SW, Davies KP, Yung E et al. c-MYC interacts with INI1/hSNF5 and requires the SWI/SNF complex for transacti-vation function. Nature Genet 1999;22:102-5.
48. Caramel J, Quignon F, Delattre O. RhoA-dependent regulation of cell migration by the tumor suppressor hSNF5/INI1. Cancer Res 2008;68:6154-61.
49. Wilson BG, Roberts CW. SWI/SNF nucleosome remodellers and cancer. Nat Rev Cancer 2011;11:481-92.
50. Euskirchen G, Auerbach RK, Snyder M. SWI/SNF chromatin-remodeling factors: multiscale analyses and diverse functions. J Biol Chem 2012;287:30897-905.
51. Reisman D, Glaros S, Thompson EA. The SWI/SNF complex and cancer. Oncogene 2009;28:1653-68.
52. Wu JI, Lessard J, Crabtree GR. Understanding the words of chromatin regulation. Cell 2009;136:200-6.
53. Shain AH, Pollack JR. The spectrum of SWI/SNF mutations, ubiquitous in human cancers. PLOS ONE 2013;8: e55119.
54. Medina PP, Romero OA, Kohno T et al. Frequent BRG1/SMARCA4-inactivating mutations in human lung cancer cell lines. Hum Mutat 2008;29:617-22.
55. Imielinski M, Berger AH, Hammerman PS et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 2012;150:1107-20.
56. Love C, Sun Z, Jima D et al. The genetic landscape of mutations in Burkitt lymphoma. Nat Genet 2012;44:1321-5.
57. Robinson G, Parker M, Kranenburg TA et al. Novel mutations target distinct subgroups of medulloblastoma. Nature 2012;488:43-8.
58. Pugh TJ, Weeraratne SD, Archer TC et al. Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations. Nature 2012;488:106-10.
59. Northcott PA, Korshunov A, Pfister SM et al. The clinical implications of medulloblastoma subgroups. Nat Rev Neurol 2012;8:340-51.
60. Dulak AM, Stojanov P, Peng S et al. Exome and whole-genome sequencing of esophageal adenocarcinoma identifies recurrent driver events and mutational complexity. Nat Genet 2013;45:478-86.
61. Oike T, Ogiwara H, Tominaga Y et al. A synthetic lethality-based strategy to treat cancers harboring a genetic deficiency in the chromatin remodeling factor BRG1. Cancer Res 2013;73:5508-18.
62. Fukuoka J, Fujii T, Shih JH et al. Chromatin remodeling factors and BRM/BRG1 expression as prognostic indicators in non-small cell lung cancer. Clin Cancer Res 2004;10: 4314-24.
63. Reisman DN, Sciarrotta J, Wang W et al. Loss of BRG1/BRM in human lung cancer cell lines and primary lung cancers: correlation with poor prognosis. Cancer Res 2003; 63:560-6.
64. Schneppenheim R, Fruhwald MC, Gesk S et al. Germline nonsense mutation and somatic inactivation of SMARCA4/BRG1 in a family with rhabdoid tumor predisposition syndrome. Am J Hum Genet 2010;86:279-84.
65. Glaros S, Cirrincione GM, Muchardt C et al. The reversible epigenetic silencing of BRM: implications for clinical targeted therapy. Oncogene 2007;26:7058-66.
66. Yamamichi N, Inada K, Ichinose M et al. Frequent loss of Brm expression in gastric cancer correlates with histologic features and differentiation state. Cancer Res 2007;67: 10727-35.
67. Shen H, Powers N, Saini N et al. The SWI/SNF ATPase Brm is a gatekeeper of proliferative control in prostate cancer. Cancer Res 2008;68:10154-62.
68. Versteege I, Sevenet N, Lange J et al. Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer. Nature 1998;394:203-6.
69. Biegel JA, Zhou JY, Rorke LB et al. Germ-line and acquired mutations of INI1 in atypical teratoid and rhabdoid tumors. Cancer Res 1999;59:74-9.
70. van den Munckhof P, Christiaans I, Kenter SB et al. Germline SMARCB1 mutation predisposes to multiple men-ingiomas and schwannomas with preferential location of cranial meningiomas at the falx cerebri. Neurogenetics 2012; 13:1-7.
71. Christiaans I, Kenter SB, Brink HC et al. Germline SMARCB1 mutation and somatic NF2 mutations in familial multiple meningiomas. J Med Genet 2011;48:93-7.
72. Hulsebos TJ, Plomp AS, Wolterman RA et al. Germline mutation of INI1/SMARCB1 in familial schwannomatosis. Am J Hum Genet 2007;80:805-10.
73. Williams BO, Remington L, Albert DM et al. Cooperative tumorigenic effects of germline mutations in Rb and p53. Nat Genet 1994;7:480-4.
74. Manda R, Kohno T, Hamada K et al. Absence of hSNF5/INI1 mutation in human lung cancer. Cancer Lett 2000;153:57-61.
75. Jones S, Wang TL, Shih Ie M et al. Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science 2010;330:228-31.
76. Wiegand KC, Shah SP, Al-Agha OM et al. ARID1A mutations in endometriosis-associated ovarian carcinomas. N Engl J Med 2010;363:1532-43.
77. Varela I, Tarpey P, Raine K et al. Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma. Nature 2011;469:539-42.
78. Fujimoto A, Totoki Y, Abe T et al. Whole-genome sequencing of liver cancers identifies etiological influences on mutation patterns and recurrent mutations in chromatin regulators. Nat Genet 2012;44:760-4.
79. Gui Y, Guo G, Huang Y et al. Frequent mutations of chroma-tin remodeling genes in transitional cell carcinoma of the bladder. Nat Genet 2011;43:875-8.
80. Zang ZJ, Cutcutache I, Poon SL et al. Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes. Nat Genet 2012;44:570-4.
81. Le Gallo M, O Hara AJ, Rudd ML et al. Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes. Nat Genet 2012;44:1310-5.
82. Sausen M, Leary RJ, Jones S et al. Integrated genomic analyses identify ARID1A and ARID1B alterations in the childhood cancer neuroblastoma. Nat Genet 2013;45:12-7.
83. Biankin AV, Waddell N, Kassahn KS et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature 2012;491:399-405.
84. Hodis E, Watson IR, Kryukov GV et al. A landscape of driver mutations in melanoma. Cell 2012;150:251-63.
85. Parsons DW, Li M, Zhang X et al. The genetic landscape of the childhood cancer medulloblastoma. Science 2011;331:435-9.
86. Stephens PJ, Tarpey PS, Davies H et al. The landscape of cancer genes and mutational processes in breast cancer. Nature 2012;486:400-4.
87. Li M, Zhao H, Zhang X et al. Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma. Nat Genet 2011;43:828-9.
88. Xia W, Nagase S, Montia AG et al. BAF180 is a critical regulator of p21 induction and a tumor suppressor mutated in breast cancer. Cancer Res 2008;68:1667-74.
89. Pasqualucci L, Dominguez-Sola D, Chiarenza A et al. Inactivating mutations of acetyltransferase genes in B-cell lymphoma. Nature 2011;471:189-95.
90. Mullighan CG, Zhang J, Kasper LH et al. CREBBP mutations in relapsed acute lymphoblastic leukaemia. Nature 2011;471:235-9.
91. Peifer M, Fernandez-Cuesta L, Sos ML et al. Integrative genome analyses identify key somatic driver mutations of small-cell lung cancer. Nat Genet 2012;44:1104-10.
92. Kishimoto M, Kohno T, Okudela K et al. Mutations and deletions of the CBP gene in human lung cancer. Clin Cancer Res 2005;11:512-9.
93. Gayther SA, Batley SJ, Linger L et al. Mutations truncating the Ep300 acetylase in human cancers. Nat Genet 2000;24: 300-3.
94. Muntean AG, Hess JL. The pathogenesis of mixed-lineage leukemia. Annu Rev Pathol 2012;7:283-301.
95. Morin RD, Johnson NA, Severson TM et al. Somatic mutation of EZH2 (Y641) in follicular and diffuse large B-cell lymphomas of germinal center origin. Nat Genet 2010;42: 181-5.
96. McCabe MT, Graves AP, Ganji G et al. Mutation of A677 in histone methyltransferase EZH2 in human B-cell lymphoma promotes hypertrimethylation of histone H3 on lysine 27 (H3K27). Proc Natl Acad Sci USA 2012;109:2989-94.
97. Ernst T, Chase AJ, Score J et al. Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nat Genet 2010;42:722-6.
98. Dalgliesh GL, Furge K, Greenman C et al. Systematic sequencing of renal carcinoma reveals inactivation of histone modifying genes. Nature 2010;463:360-3.
99. van Haaften G, Dalgliesh GL, Davies H et al. Somatic mutations of the histone H3K27 demethylase gene UTX in human cancer. Nat Genet 2009;41:521-3.
100. Lovly CM, Carbone DP. Lung cancer in 2010: one size does not fit all. Nat Rev Clin Oncol 2011;8:68-70.
101. Takeuchi K, Soda M, Togashi Y et al. RET, ROS1 and ALK fusions in lung cancer. Nat Med 2012;18:378-81.
102. Lipson D, Capelletti M, Yelensky R et al. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nat Med 2012;18:382-4.
103. Kohno T, Ichikawa H, Totoki Y et al. KIF5B-RET fusions in lung adenocarcinoma. Nat Med 2012;18:375-7.
104. Kohno T, Tsuta K, Tsuchihara K et al. RET fusion gene: translation to personalized lung cancer therapy. Cancer Sci 2013;104:1396-400.
105. Chan DA, Giaccia AJ. Harnessing synthetic lethal interactions in anticancer drug discovery. Nat Rev Drug Discov 2011;10:351-64.
106. Daigle SR, Olhava EJ, Therkelsen CA et al. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell 2011;20:53-65.
107. Daigle SR, Olhava EJ, Therkelsen CA et al. Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood 2013;122:1017-25.
108. Sneeringer CJ, Scott MP, Kuntz KW et al. Coordinated activities of wild-type plus mutant EZH2 drive tumor-associated hypertrimethylation of lysine 27 on histone H3 (H3K27) in human B-cell lymphomas. Proc Natl Acad Sci USA 2010;107:20980-5.
109. Yap DB, Chu J, Berg T et al. Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethyla-tion. Blood 2011;117:2451-9.
110. McCabe MT, Ott HM, Ganji G et al. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature 2012;492:108-12.
111. Qi W, Chan H, Teng L et al. Selective inhibition of Ezh2 by a small molecule inhibitor blocks tumor cells proliferation. Proc Natl Acad Sci USA 2012;109:21360-5.
112. Knutson SK, Wigle TJ, Warholic NM et al. A selective inhibitor of EZH2 blocks H3K27 methylation and kills mutant lymphoma cells. Nat Chem Biol 2012;8:890-6.
113. Neff T, Sinha AU, Kluk MJ et al. Polycomb repressive complex 2 is required for MLL-AF9 leukemia. Proc Natl Acad Sci USA 2012;109:5028-33.
114. Shi J, Wang E, Zuber J et al. The polycomb complex PRC2 supports aberrant self-renewal in a mouse model of MLL-AF9;Nras (G12D) acute myeloid leukemia. Oncogene 2013;32:930-8.
115. Kim W, Bird GH, Neff T et al. Targeted disruption of the EZH2-EED complex inhibits EZH2-dependent cancer. Nat Chem Biol 2013;9:643-50.
116. Copeland RA, Solomon ME, Richon VM. Protein methyl-transferases as a target class for drug discovery. Nat Rev Drug Discov 2009;8:724-32.
117. Harris CC, Hollstein M. Clinical implications of the p53 tumor-suppressor gene. N Engl J Med 1993;329:1318-27.
118. Olivier M, Petitjean A, Marcel V et al. Recent advances in p53 research: an interdisciplinary perspective. Cancer Gene Ther 2009;16:1-12.
119. Liu TC, Hwang TH, Bell JC et al. Translation of targeted onco-lytic virotherapeutics from the lab into the clinic, and back again: a high-value iterative loop. Mol Ther 2008;16:1006-8.
120. Bryant HE, Schultz N, Thomas HD et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 2005;434:913-7.
121. Farmer H, McCabe N, Lord CJ et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 2005;434:917-21.
122. Fong PC, Boss DS, Yap TA et al. Inhibition of poly (ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med 2009;361:123-34.
123. Muller FL, Colla S, Aquilanti E et al. Passenger deletions generate therapeutic vulnerabilities in cancer. Nature 2012; 488:337-42.
124. Chan DA, Sutphin PD, Nguyen P et al. Targeting GLUT1 and the Warburg effect in renal cell carcinoma by chemical synthetic lethality. Sci Transl Med 2011;3:94ra70.
125. Martin SA, McCabe N, Mullarkey M et al. DNA polymerases as potential therapeutic targets for cancers deficient in the DNA mismatch repair proteins MSH2 or MLH1. Cancer Cell 2010;17:235-48.
126. Knutson SK, Warholic NM, Wigle TJ et al. Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2. Proc Natl Acad Sci USA 2013;110:7922-7.
127. Reyes JC, Barra J, Muchardt C et al. Altered control of cellular proliferation in the absence of mammalian brahma (SNF2α). EMBO J 1998;17:6979-91.
128. Alimova I, Birks DK, Harris PS et al. Inhibition of EZH2 suppresses self-renewal and induces radiation sensitivity in atypical rhabdoid teratoid tumor cells. Neuro Oncol 2013;15:149-60.
129. Roberts CW, Biegel JA. The role of SMARCB1/INI1 in development of rhabdoid tumor. Cancer Biol Ther 2009;8:412-6.
130. Jagani Z, Mora-Blanco EL, Sansam CG et al. Loss of the tumor suppressor Snf5 leads to aberrant activation of the Hedgehog-Gli pathway. Nat Med 2010;16:1429-33.
131. Ginn KF, Gajjar A. Atypical teratoid rhabdoid tumor: current therapy and future directions. Front Oncol 2012;2:114.
132. Moyer MW. First drugs found to inhibit elusive cancer target. Nat Med 2011;17:1325.
133. Zuber J, Shi J, Wang E et al. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia. Nature 2011;478:524-8.
134. Mertz JA, Conery AR, Bryant BM et al. Targeting MYC dependence in cancer by inhibiting BET bromodomains. Proc Natl Acad Sci USA 2011;108:16669-74.
135. Delmore JE, Issa GC, Lemieux ME et al. BET bromodomain inhibition as a therapeutic strategy to target c-Myc. Cell 2011;146:904-17.
136. Dawson MA, Prinjha RK, Dittmann A et al. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature 2011;478:529-33.
137. Filippakopoulos P, Qi J, Picaud S et al. Selective inhibition of BET bromodomains. Nature 2010;468:1067-73.
138. Lovén J, Hoke HA, Lin CY et al. Selective inhibition of tumor oncogenes by disruption of super-enhancers. Cell 2013;153:320-34.
139. Boyle P, Leon B. World Cancer Report 2008. Lyon: International Agency for Research on Cancer, World Health Organization, 2008.
140. Shiraishi K, Kunitoh H, Daigo Y et al. A genome-wide association study identifies two new susceptibility loci for lung adenocarcinoma in the Japanese population. Nat Genet 2012;44:900-3.