Trial watch–inhibiting PARP enzymes for anticancer therapy

Molecular and Cellular Oncology

Volumn 3, Issue 2, 2016, Pages

  Sistigu, Antonella ^a   Manic, Gwenola ^a   Obrist, Florine ^b,c,d,e   Vitale, Ilio ^a,f  

^a REGINA ELENA NATIONAL CANCER INSTITUTE   (Italy)

^b UNIVERSITÉ PARIS SACLAY   (France)

^c INSERM   (France)

^d CENTRE DE RECHERCHE DES CORDELIERS   (France)

^e INSTITUT GUSTAVE ROUSSY   (France)

^f UNIVERSITY OF ROME TOR VERGATA   (Italy)

Author keywords

Cell death; DNA damage; drug resistance; metabolism; NAD; olaparib; synthetic lethality

Indexed keywords

EID: 84988473473     PISSN: None     EISSN: 23723556     Source Type: Journal    
DOI: 10.1080/23723556.2015.1053594     Document Type: Review

References (330)

1. Gibson BA, Kraus WL. New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs. Nat Rev Mol Cell Biol 2012; 13:411-24; PMID:22713970; http://dx.doi.org/10.1038/nrm3376
2. Schreiber V, Dantzer F, Ame JC, de Murcia G. Poly(ADP-ribose): novel functions for an old molecule. Nat Rev Mol Cell Biol 2006; 7:517-28; PMID:16829982; http://dx.doi.org/10.1038/nrm1963
3. D‘Amours D, Desnoyers S, D’Silva I, Poirier GG. Poly(ADP-ribosyl)ation reactions in the regulation of nuclear functions. Biochem J 1999; 342 (Pt 2):249-68; PMID:10455009; http://dx.doi.org/10.1042/0264-6021:3420249
4. Durkacz BW, Omidiji O, Gray DA, Shall S. (ADP-ribose)n participates in DNA excision repair. Nature 1980; 283:593-6; PMID:6243744; http://dx.doi.org/10.1038/283593a0
5. Burkle A. Poly(ADP-ribose). The most elaborate metabolite of NAD+. FEBS J 2005; 272:4576-89; PMID:16156780; http://dx.doi.org/10.1111/j.1742-4658.2005.04864.x
6. Vyas S, Chang P. New PARP targets for cancer therapy. Nat Rev Cancer 2014; 14:502-9; PMID:24898058; http://dx.doi.org/10.1038/nrc3748
7. Hottiger MO, Hassa PO, Luscher B, Schuler H, Koch-Nolte F. Toward a unified nomenclature for mammalian ADP-ribosyltransferases. Trends Biochem Sci 2010; 35:208-19; PMID:20106667; http://dx.doi.org/10.1016/j.tibs.2009.12.003
8. Li M, Yu X. The role of poly(ADP-ribosyl)ation in DNA damage response and cancer chemotherapy. Oncogene 2015; 34(26):3349-56; PMID:25220415; http://dx.doi.org/10.1038/onc.2014.295
9. Masutani M, Fujimori H. Poly(ADP-ribosyl)ation in carcinogenesis. Mol Aspects Med 2013; 34:1202-16; PMID:23714734; http://dx.doi.org/10.1016/j.mam.2013.05.003
10. Burkle A, Virag L. Poly(ADP-ribose): PARadigms and PARadoxes. Mol Aspects Med 2013; 34:1046-65; PMID:23290998; http://dx.doi.org/10.1016/j.mam.2012.12.010
11. Bai P, Canto C. The role of PARP-1 and PARP-2 enzymes in metabolic regulation and disease. Cell Metab 2012; 16:290-5; PMID:22921416; http://dx.doi.org/10.1016/j.cmet.2012.06.016
12. Davar D, Beumer JH, Hamieh L, Tawbi H. Role of PARP inhibitors in cancer biology and therapy. Curr Med Chem 2012; 19:3907-21; PMID:22788767; http://dx.doi.org/10.2174/092986712802002464
13. Leung AK. Poly(ADP-ribose): an organizer of cellular architecture. J Cell Biol 2014; 205:613-9; PMID:24914234; http://dx.doi.org/10.1083/jcb.201402114
14. Luo X, Kraus WL. On PAR with PARP: cellular stress signaling through poly(ADP-ribose) and PARP-1. Genes Dev 2012; 26:417-32; PMID:22391446; http://dx.doi.org/10.1101/gad.183509.111
15. Ame JC, Spenlehauer C, de Murcia G. The PARP superfamily. Bioessays 2004; 26:882-93; PMID:15273990; http://dx.doi.org/10.1002/bies.20085
16. Rouleau M, Patel A, Hendzel MJ, Kaufmann SH, Poirier GG. PARP inhibition: PARP1 and beyond. Nat Rev Cancer 2010; 10:293-301; PMID:20200537; http://dx.doi.org/10.1038/nrc2812
17. Ciccia A, Elledge SJ. The DNA damage response: making it safe to play with knives. Mol Cell 2010; 40:179-204; PMID:20965415; http://dx.doi.org/10.1016/j.molcel.2010.09.019
18. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144:646-74; PMID:21376230; http://dx.doi.org/10.1016/j.cell.2011.02.013
19. Giglia-Mari G, Zotter A, Vermeulen W. DNA damage response. Cold Spring Harb Perspect Biol 2011; 3:a000745; PMID:20980439; http://dx.doi.org/10.1101/cshperspect.a000745
20. Jackson SP, Bartek J. The DNA-damage response in human biology and disease. Nature 2009; 461:1071-8; PMID:19847258; http://dx.doi.org/10.1038/nature08467
21. Harper JW, Elledge SJ. The DNA damage response: ten years after. Mol Cell 2007; 28:739-45; PMID:18082599; http://dx.doi.org/10.1016/j.molcel.2007.11.015
22. Beck C, Robert I, Reina-San-Martin B, Schreiber V, Dantzer F. Poly(ADP-ribose) polymerases in double-strand break repair: focus on PARP1, PARP2 and PARP3. Exp Cell Res 2014; 329:18-25; PMID:25017100; http://dx.doi.org/10.1016/j.yexcr.2014.07.003
23. Papeo G, Forte B, Orsini P, Perrera C, Posteri H, Scolaro A, Montagnoli A. Poly(ADP-ribose) polymerase inhibition in cancer therapy: are we close to maturity? Expert Opin Ther Pat 2009; 19:1377-400; PMID:19743897; http://dx.doi.org/10.1517/13543770903215883
24. Ali AA, Timinszky G, Arribas-Bosacoma R, Kozlowski M, Hassa PO, Hassler M, Ladurner AG, Pearl LH, Oliver AW. The zinc-finger domains of PARP1 cooperate to recognize DNA strand breaks. Nat Struct Mol Biol 2012; 19:685-92; PMID:22683995; http://dx.doi.org/10.1038/nsmb.2335
25. Okano S, Lan L, Caldecott KW, Mori T, Yasui A. Spatial and temporal cellular responses to single-strand breaks in human cells. Mol Cell Biol 2003; 23:3974-81; PMID:12748298; http://dx.doi.org/10.1128/MCB.23.11.3974-3981.2003
26. De Vos M, Schreiber V, Dantzer F. The diverse roles and clinical relevance of PARPs in DNA damage repair: current state of the art. Biochem Pharmacol 2012; 84:137-46; PMID:22469522; http://dx.doi.org/10.1016/j.bcp.2012.03.018
27. El-Khamisy SF, Masutani M, Suzuki H, Caldecott KW. A requirement for PARP-1 for the assembly or stability of XRCC1 nuclear foci at sites of oxidative DNA damage. Nucleic Acids Res 2003; 31:5526-33; PMID:14500814; http://dx.doi.org/10.1093/nar/gkg761
28. Masson M, Niedergang C, Schreiber V, Muller S, Menissier-de Murcia J, de Murcia G. XRCC1 is specifically associated with poly(ADP-ribose) polymerase and negatively regulates its activity following DNA damage. Mol Cell Biol 1998; 18:3563-71; PMID:9584196
29. Li M, Lu LY, Yang CY, Wang S, Yu X. The FHA and BRCT domains recognize ADP-ribosylation during DNA damage response. Genes Dev 2013; 27:1752-68; PMID:23964092; http://dx.doi.org/10.1101/gad.226357.113
30. Pleschke JM, Kleczkowska HE, Strohm M, Althaus FR. Poly(ADP-ribose) binds to specific domains in DNA damage checkpoint proteins. J Biol Chem 2000; 275:40974-80; PMID:11016934; http://dx.doi.org/10.1074/jbc.M006520200
31. Fisher AE, Hochegger H, Takeda S, Caldecott KW. Poly(ADP-ribose) polymerase 1 accelerates single-strand break repair in concert with poly(ADP-ribose) glycohydrolase. Mol Cell Biol 2007; 27:5597-605; PMID:17548475; http://dx.doi.org/10.1128/MCB.02248-06
32. Robu M, Shah RG, Petitclerc N, Brind'Amour J, Kandan-Kulangara F, Shah GM. Role of poly(ADP-ribose) polymerase-1 in the removal of UV-induced DNA lesions by nucleotide excision repair. Proc Natl Acad Sci U S A 2013; 110:1658-63; PMID:23319653; http://dx.doi.org/10.1073/pnas.1209507110
33. Pines A, Vrouwe MG, Marteijn JA, Typas D, Luijsterburg MS, Cansoy M, Hensbergen P, Deelder A, de Groot A, Matsumoto S, et al. PARP1 promotes nucleotide excision repair through DDB2 stabilization and recruitment of ALC1. J Cell Biol 2012; 199:235-49; PMID:23045548; http://dx.doi.org/10.1083/jcb.201112132
34. Audebert M, Salles B, Calsou P. Effect of double-strand break DNA sequence on the PARP-1 NHEJ pathway. Biochem Biophys Res Commun 2008; 369:982-8; PMID:18054777; http://dx.doi.org/10.1016/j.bbrc.2007.11.132
35. Wang M, Wu W, Rosidi B, Zhang L, Wang H, Iliakis G. PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways. Nucleic Acids Res 2006; 34:6170-82; PMID:17088286; http://dx.doi.org/10.1093/nar/gkl840
36. Bryant HE, Petermann E, Schultz N, Jemth AS, Loseva O, Issaeva N, Johansson F, Fernandez S, McGlynn P, Helleday T. PARP is activated at stalled forks to mediate Mre11-dependent replication restart and recombination. EMBO J 2009; 28:2601-15; PMID:19629035; http://dx.doi.org/10.1038/emboj.2009.206
37. Sugimura K, Takebayashi S, Taguchi H, Takeda S, Okumura K. PARP-1 ensures regulation of replication fork progression by homologous recombination on damaged DNA. J Cell Biol 2008; 183:1203-12; PMID:19103807; http://dx.doi.org/10.1083/jcb.200806068
38. Li M, Yu X. Function of BRCA1 in the DNA damage response is mediated by ADP-ribosylation. Cancer Cell 2013; 23:693-704; PMID:23680151; http://dx.doi.org/10.1016/j.ccr.2013.03.025
39. Hu Y, Petit SA, Ficarro SB, Toomire KJ, Xie A, Lim E, Cao SA, Park E, Eck MJ, Scully R, et al. PARP1-driven poly-ADP-ribosylation regulates BRCA1 function in homologous recombination-mediated DNA repair. Cancer Discov 2014; 4:1430-47; PMID:25252691; http://dx.doi.org/10.1158/2159-8290.CD-13-0891
40. Langelier MF, Planck JL, Roy S, Pascal JM. Structural basis for DNA damage-dependent poly(ADP-ribosyl)ation by human PARP-1. Science 2012; 336:728-32; PMID:22582261; http://dx.doi.org/10.1126/science.1216338
41. Alvarez-Gonzalez R, Pacheco-Rodriguez G, Mendoza-Alvarez H. Enzymology of ADP-ribose polymer synthesis. Mol Cell Biochem 1994; 138:33-7; PMID:7898472; http://dx.doi.org/10.1007/BF00928440
42. Langelier MF, Pascal JM. PARP-1 mechanism for coupling DNA damage detection to poly(ADP-ribose) synthesis. Curr Opin Struct Biol 2013; 23:134-43; PMID:23333033; http://dx.doi.org/10.1016/j.sbi.2013.01.003
43. Kim MY, Zhang T, Kraus WL. Poly(ADP-ribosyl)ation by PARP-1: ‘PAR-laying’ NAD+ into a nuclear signal. Genes Dev 2005; 19:1951-67; PMID:16140981; http://dx.doi.org/10.1101/gad.1331805
44. Haince JF, McDonald D, Rodrigue A, Dery U, Masson JY, Hendzel MJ, Poirier GG. PARP1-dependent kinetics of recruitment of MRE11 and NBS1 proteins to multiple DNA damage sites. J Biol Chem 2008; 283:1197-208; PMID:18025084; http://dx.doi.org/10.1074/jbc.M706734200
45. Hassa PO, Hottiger MO. The diverse biological roles of mammalian PARPS, a small but powerful family of poly-ADP-ribose polymerases. Front Biosci 2008; 13:3046-82; PMID:17981777; http://dx.doi.org/10.2741/2909
46. Martinez-Zamudio R, Ha HC. Histone ADP-ribosylation facilitates gene transcription by directly remodeling nucleosomes. Mol Cell Biol 2012; 32:2490-502; PMID:22547677; http://dx.doi.org/10.1128/MCB.06667-11
47. Messner S, Hottiger MO. Histone ADP-ribosylation in DNA repair, replication and transcription. Trends Cell Biol 2011; 21:534-42; PMID:21741840; http://dx.doi.org/10.1016/j.tcb.2011.06.001
48. Kulkarni A, Oza J, Yao M, Sohail H, Ginjala V, Tomas-Loba A, Horejsi Z, Tan AR, Boulton SJ, Ganesan S. Tripartite Motif-containing 33 (TRIM33) protein functions in the poly(ADP-ribose) polymerase (PARP)-dependent DNA damage response through interaction with Amplified in Liver Cancer 1 (ALC1) protein. J Biol Chem 2013; 288:32357-69; PMID:23926104; http://dx.doi.org/10.1074/jbc.M113.459164
49. Kraus WL. New functions for an ancient domain. Nat Struct Mol Biol 2009; 16:904-7; PMID:19739287; http://dx.doi.org/10.1038/nsmb0909-904
50. Timinszky G, Till S, Hassa PO, Hothorn M, Kustatscher G, Nijmeijer B, Colombelli J, Altmeyer M, Stelzer EH, Scheffzek K, et al. A macrodomain-containing histone rearranges chromatin upon sensing PARP1 activation. Nat Struct Mol Biol 2009; 16:923-9; PMID:19680243; http://dx.doi.org/10.1038/nsmb.1664
51. Gottschalk AJ, Timinszky G, Kong SE, Jin J, Cai Y, Swanson SK, Washburn MP, Florens L, Ladurner AG, Conaway JW, et al. Poly(ADP-ribosyl)ation directs recruitment and activation of an ATP-dependent chromatin remodeler. Proc Natl Acad Sci U S A 2009; 106:13770-4; PMID:19666485; http://dx.doi.org/10.1073/pnas.0906920106
52. Ahel D, Horejsi Z, Wiechens N, Polo SE, Garcia-Wilson E, Ahel I, Flynn H, Skehel M, West SC, Jackson SP, et al. Poly(ADP-ribose)-dependent regulation of DNA repair by the chromatin remodeling enzyme ALC1. Science 2009; 325:1240-3; PMID:19661379; http://dx.doi.org/10.1126/science.1177321
53. Gagne JP, Isabelle M, Lo KS, Bourassa S, Hendzel MJ, Dawson VL, Dawson TM, Poirier GG. Proteome-wide identification of poly(ADP-ribose) binding proteins and poly(ADP-ribose)-associated protein complexes. Nucleic Acids Res 2008; 36:6959-76; PMID:18981049; http://dx.doi.org/10.1093/nar/gkn771
54. Malanga M, Althaus FR. The role of poly(ADP-ribose) in the DNA damage signaling network. Biochem Cell Biol 2005; 83:354-64; PMID:15959561; http://dx.doi.org/10.1139/o05-038
55. Tulin A, Spradling A. Chromatin loosening by poly(ADP)-ribose polymerase (PARP) at Drosophila puff loci. Science 2003; 299:560-2; PMID:12543974; http://dx.doi.org/10.1126/science.1078764
56. Poirier GG, de Murcia G, Jongstra-Bilen J, Niedergang C, Mandel P. Poly(ADP-ribosyl)ation of polynucleosomes causes relaxation of chromatin structure. Proc Natl Acad Sci U S A 1982; 79:3423-7; PMID:6808510; http://dx.doi.org/10.1073/pnas.79.11.3423
57. Ogata N, Ueda K, Kagamiyama H, Hayaishi O. ADP-ribosylation of histone H1. Identification of glutamic acid residues 2, 14, and the COOH-terminal lysine residue as modification sites. J Biol Chem 1980; 255:7616-20; PMID:6772638
58. Oka S, Kato J, Moss J. Identification and characterization of a mammalian 39-kDa poly(ADP-ribose) glycohydrolase. J Biol Chem 2006; 281:705-13; PMID:16278211; http://dx.doi.org/10.1074/jbc.M510290200
59. Meyer-Ficca ML, Meyer RG, Coyle DL, Jacobson EL, Jacobson MK. Human poly(ADP-ribose) glycohydrolase is expressed in alternative splice variants yielding isoforms that localize to different cell compartments. Exp Cell Res 2004; 297:521-32; PMID:15212953; http://dx.doi.org/10.1016/j.yexcr.2004.03.050
60. Sharifi R, Morra R, Appel CD, Tallis M, Chioza B, Jankevicius G, Simpson MA, Matic I, Ozkan E, Golia B, et al. Deficiency of terminal ADP-ribose protein glycohydrolase TARG1/C6orf130 in neurodegenerative disease. EMBO J 2013; 32:1225-37; PMID:23481255; http://dx.doi.org/10.1038/emboj.2013.51
61. David KK, Andrabi SA, Dawson TM, Dawson VL. Parthanatos, a messenger of death. Front Biosci (Landmark Ed) 2009; 14:1116-28; PMID:19273119; http://dx.doi.org/10.2741/3297
62. Aredia F, Scovassi AI. Poly(ADP-ribose): a signaling molecule in different paradigms of cell death. Biochem Pharmacol 2014; 92:157-63; PMID:24976506; http://dx.doi.org/10.1016/j.bcp.2014.06.021
63. Wang Y, Kim NS, Haince JF, Kang HC, David KK, Andrabi SA, Poirier GG, Dawson VL, Dawson TM. Poly(ADP-ribose) (PAR) binding to apoptosis-inducing factor is critical for PAR polymerase-1-dependent cell death (parthanatos). Sci Signal 2011; 4:ra20; PMID:21467298
64. Wang Y, Kim NS, Li X, Greer PA, Koehler RC, Dawson VL, Dawson TM. Calpain activation is not required for AIF translocation in PARP-1-dependent cell death (parthanatos). J Neurochem 2009; 110:687-96; PMID:19457082; http://dx.doi.org/10.1111/j.1471-4159.2009.06167.x
65. Berger NA, Sims JL, Catino DM, Berger SJ. Poly(ADP-ribose) polymerase mediates the suicide response to massive DNA damage: studies in normal and DNA-repair defective cells. Princess Takamatsu Symp 1983; 13:219-26; PMID:6317637
66. Andrabi SA, Kang HC, Haince JF, Lee YI, Zhang J, Chi Z, West AB, Koehler RC, Poirier GG, Dawson TM, et al. Iduna protects the brain from glutamate excitotoxicity and stroke by interfering with poly(ADP-ribose) polymer-induced cell death. Nat Med 2011; 17:692-9; PMID:21602803; http://dx.doi.org/10.1038/nm.2387
67. Manic G, Obrist F, Kroemer G, Vitale I, Galluzzi L. Chloroquine and hydroxychloroquine for cancer therapy. Mol Cell Oncol 2014; 1:e29911; http://dx.doi.org/10.4161/mco.29911
68. Obrist F, Manic G, Kroemer G, Vitale I, Galluzzi L. Trial Watch: Proteasomal inhibitors for anticancer therapy. Mol Cell Oncol 2014; 2:e974463; http://dx.doi.org/10.4161/23723556.2014.974463
69. Tong WM, Hande MP, Lansdorp PM, Wang ZQ. DNA strand break-sensing molecule poly(ADP-Ribose) polymerase cooperates with p53 in telomere function, chromosome stability, and tumor suppression. Mol Cell Biol 2001; 21:4046-54; PMID:11359911; http://dx.doi.org/10.1128/MCB.21.12.4046-4054.2001
70. Trucco C, Oliver FJ, de Murcia G, Menissier-de Murcia J. DNA repair defect in poly(ADP-ribose) polymerase-deficient cell lines. Nucleic Acids Res 1998; 26:2644-9; PMID:9592149; http://dx.doi.org/10.1093/nar/26.11.2644
71. Nicolas L, Martinez C, Baro C, Rodriguez M, Baroja-Mazo A, Sole F, Flores JM, Ampurdanes C, Dantzer F, Martin-Caballero J, et al. Loss of poly(ADP-ribose) polymerase-2 leads to rapid development of spontaneous T-cell lymphomas in p53-deficient mice. Oncogene 2010; 29:2877-83; PMID:20154718; http://dx.doi.org/10.1038/onc.2010.11
72. Menissier de Murcia J, Ricoul M, Tartier L, Niedergang C, Huber A, Dantzer F, Schreiber V, Ame JC, Dierich A, LeMeur M, et al. Functional interaction between PARP-1 and PARP-2 in chromosome stability and embryonic development in mouse. EMBO J 2003; 22:2255-63; PMID:12727891; http://dx.doi.org/10.1093/emboj/cdg206
73. Tong WM, Yang YG, Cao WH, Galendo D, Frappart L, Shen Y, Wang ZQ. Poly(ADP-ribose) polymerase-1 plays a role in suppressing mammary tumourigenesis in mice. Oncogene 2007; 26:3857-67; PMID:17160013; http://dx.doi.org/10.1038/sj.onc.1210156
74. Tong WM, Cortes U, Hande MP, Ohgaki H, Cavalli LR, Lansdorp PM, Haddad BR, Wang ZQ. Synergistic role of Ku80 and poly(ADP-ribose) polymerase in suppressing chromosomal aberrations and liver cancer formation. Cancer Res 2002; 62:6990-6; PMID:12460917
75. Sonnenblick A, de Azambuja E, Azim HA, Jr., Piccart M. An update on PARP inhibitors–moving to the adjuvant setting. Nat Rev Clin Oncol 2015; 12:27-41; PMID:25286972; http://dx.doi.org/10.1038/nrclinonc.2014.163
76. Morrison C, Smith GC, Stingl L, Jackson SP, Wagner EF, Wang ZQ. Genetic interaction between PARP and DNA-PK in V(D)J recombination and tumorigenesis. Nat Genet 1997; 17:479-82; PMID:9398855; http://dx.doi.org/10.1038/ng1297-479
77. Piskunova TS, Yurova MN, Ovsyannikov AI, Semenchenko AV, Zabezhinski MA, Popovich IG, Wang ZQ, Anisimov VN. Deficiency in Poly(ADP-ribose) Polymerase-1 (PARP-1) Accelerates Aging and Spontaneous Carcinogenesis in Mice. Curr Gerontol Geriatr Res 2008; PMID:19415146; http://dx.doi.org/10.1155/2008/754190
78. Gonzalez-Flores A, Aguilar-Quesada R, Siles E, Pozo S, Rodriguez-Lara MI, Lopez-Jimenez L, Lopez-Rodriguez M, Peralta-Leal A, Villar D, Martin-Oliva D, et al. Interaction between PARP-1 and HIF-2alpha in the hypoxic response. Oncogene 2014; 33:891-8; PMID:23455322; http://dx.doi.org/10.1038/onc.2013.9
79. Boehler C, Gauthier L, Yelamos J, Noll A, Schreiber V, Dantzer F. Phenotypic characterization of Parp-1 and Parp-2 deficient mice and cells. Methods Mol Biol 2011; 780:313-36; PMID:21870269
80. Menisser-de Murcia J, Mark M, Wendling O, Wynshaw-Boris A, de Murcia G. Early embryonic lethality in PARP-1 Atm double-mutant mice suggests a functional synergy in cell proliferation during development. Mol Cell Biol 2001; 21:1828-32; PMID:11238919; http://dx.doi.org/10.1128/MCB.21.5.1828-1832.2001
81. Huber A, Bai P, de Murcia JM, de Murcia G. PARP-1, PARP-2 and ATM in the DNA damage response: functional synergy in mouse development. DNA Repair (Amst) 2004; 3:1103-8; PMID:15279798; http://dx.doi.org/10.1016/j.dnarep.2004.06.002
82. Ogawa K, Masutani M, Kato K, Tang M, Kamada N, Suzuki H, Nakagama H, Sugimura T, Shirai T. Parp-1 deficiency does not enhance liver carcinogenesis induced by 2-amino-3-methylimidazo; [4,5-f]quinoline in mice. Cancer Lett 2006; 236:32-8; PMID:15955622; http://dx.doi.org/10.1016/j.canlet.2005.04.030
83. Gunji A, Uemura A, Tsutsumi M, Nozaki T, Kusuoka O, Omura K, Suzuki H, Nakagama H, Sugimura T, Masutani M. Parp-1 deficiency does not increase the frequency of tumors in the oral cavity and esophagus of ICR/129Sv mice by 4-nitroquinoline 1-oxide, a carcinogen producing bulky adducts. Cancer Lett 2006; 241:87-92; PMID:16338061; http://dx.doi.org/10.1016/j.canlet.2005.10.003
84. Shibata A, Kamada N, Masumura K, Nohmi T, Kobayashi S, Teraoka H, Nakagama H, Sugimura T, Suzuki H, Masutani M. Parp-1 deficiency causes an increase of deletion mutations and insertions/rearrangements in vivo after treatment with an alkylating agent. Oncogene 2005; 24:1328-37; PMID:15608683; http://dx.doi.org/10.1038/sj.onc.1208289
85. Shibata A, Maeda D, Ogino H, Tsutsumi M, Nohmi T, Nakagama H, Sugimura T, Teraoka H, Masutani M. Role of Parp-1 in suppressing spontaneous deletion mutation in the liver and brain of mice at adolescence and advanced age. Mutat Res 2009; 664:20-7; PMID:19428377; http://dx.doi.org/10.1016/j.mrfmmm.2009.02.001
86. Simbulan-Rosenthal CM, Haddad BR, Rosenthal DS, Weaver Z, Coleman A, Luo R, Young HM, Wang ZQ, Ried T, Smulson ME. Chromosomal aberrations in PARP(−/−) mice: genome stabilization in immortalized cells by reintroduction of poly(ADP-ribose) polymerase cDNA. Proc Natl Acad Sci U S A 1999; 96:13191-6; PMID:10557296; http://dx.doi.org/10.1073/pnas.96.23.13191
87. Piskunova TS, Zabezhinskii MA, Popovich IG, Tyndyk ML, Iurova MN, Anisimov VN.; [Diethylnitrosamine-induced carcinogenesis in PARP-1(−/−) and PARP-1(+/+) mice]. Vopr Onkol 2009; 55:608-11; PMID:20020658
88. Tsutsumi M, Masutani M, Nozaki T, Kusuoka O, Tsujiuchi T, Nakagama H, Suzuki H, Konishi Y, Sugimura T. Increased susceptibility of poly(ADP-ribose) polymerase-1 knockout mice to nitrosamine carcinogenicity. Carcinogenesis 2001; 22:1-3; PMID:11159733; http://dx.doi.org/10.1093/carcin/22.1.1
89. Nozaki T, Fujihara H, Watanabe M, Tsutsumi M, Nakamoto K, Kusuoka O, Kamada N, Suzuki H, Nakagama H, Sugimura T, et al. Parp-1 deficiency implicated in colon and liver tumorigenesis induced by azoxymethane. Cancer Sci 2003; 94:497-500; PMID:12824873; http://dx.doi.org/10.1111/j.1349-7006.2003.tb01472.x
90. Tanori M, Mancuso M, Pasquali E, Leonardi S, Rebessi S, Di Majo V, Guilly MN, Giangaspero F, Covelli V, Pazzaglia S, et al. PARP-1 cooperates with Ptc1 to suppress medulloblastoma and basal cell carcinoma. Carcinogenesis 2008; 29:1911-9; PMID:18660545; http://dx.doi.org/10.1093/carcin/bgn174
91. Raval-Fernandes S, Kickhoefer VA, Kitchen C, Rome LH. Increased susceptibility of vault poly(ADP-ribose) polymerase-deficient mice to carcinogen-induced tumorigenesis. Cancer Res 2005; 65:8846-52; PMID:16204055; http://dx.doi.org/10.1158/0008-5472.CAN-05-0770
92. Min W, Cortes U, Herceg Z, Tong WM, Wang ZQ. Deletion of the nuclear isoform of poly(ADP-ribose) glycohydrolase (PARG) reveals its function in DNA repair, genomic stability and tumorigenesis. Carcinogenesis 2010; 31:2058-65; PMID:20926829; http://dx.doi.org/10.1093/carcin/bgq205
93. Masutani M, Nakagama H, Sugimura T. Poly(ADP-ribosyl)ation in relation to cancer and autoimmune disease. Cell Mol Life Sci 2005; 62:769-83; PMID:15868402; http://dx.doi.org/10.1007/s00018-004-4509-x
94. Lockett KL, Hall MC, Xu J, Zheng SL, Berwick M, Chuang SC, Clark PE, Cramer SD, Lohman K, Hu JJ. The ADPRT V762A genetic variant contributes to prostate cancer susceptibility and deficient enzyme function. Cancer Res 2004; 64:6344-8; PMID:15342424; http://dx.doi.org/10.1158/0008-5472.CAN-04-0338
95. Hao B, Wang H, Zhou K, Li Y, Chen X, Zhou G, Zhu Y, Miao X, Tan W, Wei Q, et al. Identification of genetic variants in base excision repair pathway and their associations with risk of esophageal squamous cell carcinoma. Cancer Res 2004; 64:4378-84; PMID:15205355; http://dx.doi.org/10.1158/0008-5472.CAN-04-0372
96. Zhang X, Miao X, Liang G, Hao B, Wang Y, Tan W, Li Y, Guo Y, He F, Wei Q, et al. Polymorphisms in DNA base excision repair genes ADPRT and XRCC1 and risk of lung cancer. Cancer Res 2005; 65:722-6; PMID:15705867
97. Ye F, Cheng Q, Hu Y, Zhang J, Chen H. PARP-1 Val762Ala polymorphism is associated with risk of cervical carcinoma. PLoS One 2012; 7:e37446; PMID:22624032; http://dx.doi.org/10.1371/journal.pone.0037446
98. Roszak A, Lianeri M, Sowinska A, Jagodzinski PP. Involvement of PARP-1 Val762Ala polymorphism in the onset of cervical cancer in caucasian women. Mol Diagn Ther 2013; 17:239-45; PMID:23633189; http://dx.doi.org/10.1007/s40291-013-0036-5
99. Yu H, Ma H, Yin M, Wei Q. Association between PARP-1 V762A polymorphism and cancer susceptibility: a meta-analysis. Genet Epidemiol 2012; 36:56-65; PMID:22127734; http://dx.doi.org/10.1002/gepi.20663
100. Qin Q, Lu J, Zhu H, Xu L, Cheng H, Zhan L, Yang X, Zhang C, Sun X. PARP-1 Val762Ala polymorphism and risk of cancer: a meta-analysis based on 39 case-control studies. PLoS One 2014; 9:e98022; PMID:24853559; http://dx.doi.org/10.1371/journal.pone.0098022
101. Singh N. Enhanced poly ADP-ribosylation in human leukemia lymphocytes and ovarian cancers. Cancer Lett 1991; 58:131-5; PMID:1904797; http://dx.doi.org/10.1016/0304-3835(91)90035-G
102. -2 and complex chromosomal abnormalities. Hum Pathol 2014; 45:1582-7; PMID:24856976; http://dx.doi.org/10.1016/j.humpath.2013.11.024
103. Ossovskaya V, Koo IC, Kaldjian EP, Alvares C, Sherman BM. Upregulation of Poly (ADP-Ribose) Polymerase-1 (PARP1) in triple-negative breast cancer and other primary human tumor types. Genes Cancer 2010; 1:812-21; PMID:21779467; http://dx.doi.org/10.1177/1947601910383418
104. Bieche I, Pennaneach V, Driouch K, Vacher S, Zaremba T, Susini A, Lidereau R, Hall J. Variations in the mRNA expression of poly(ADP-ribose) polymerases, poly(ADP-ribose) glycohydrolase and ADP-ribosylhydrolase 3 in breast tumors and impact on clinical outcome. Int J Cancer 2013; 133:2791-800; PMID:23736962
105. Rojo F, Garcia-Parra J, Zazo S, Tusquets I, Ferrer-Lozano J, Menendez S, Eroles P, Chamizo C, Servitja S, Ramirez-Merino N, et al. Nuclear PARP-1 protein overexpression is associated with poor overall survival in early breast cancer. Ann Oncol 2012; 23:1156-64; PMID:21908496; http://dx.doi.org/10.1093/annonc/mdr361
106. Domagala P, Huzarski T, Lubinski J, Gugala K, Domagala W. PARP-1 expression in breast cancer including BRCA1-associated, triple negative and basal-like tumors: possible implications for PARP-1 inhibitor therapy. Breast Cancer Res Treat 2011; 127:861-9; PMID:21409392; http://dx.doi.org/10.1007/s10549-011-1441-2
107. Hassumi-Fukasawa MK, Miranda-Camargo FA, Zanetti BR, Galano DF, Ribeiro-Silva A, Soares EG. Expression of BAG-1 and PARP-1 in precursor lesions and invasive cervical cancer associated with human papillomavirus (HPV). Pathol Oncol Res 2012; 18:929-37; PMID:22454210; http://dx.doi.org/10.1007/s12253-012-9523-y
108. Tang Y, Wang YL, Yang L, Xu JX, Xiong W, Xiao M, Li M. Inhibition of arginine ADP-ribosyltransferase 1 reduces the expression of poly(ADP-ribose) polymerase-1 in colon carcinoma. Int J Mol Med 2013; 32:130-6; PMID:23652727
109. Yalcintepe L, Turker-Sener L, Sener A, Yetkin G, Tiryaki D, Bermek E. Changes in NAD/ADP-ribose metabolism in rectal cancer. Braz J Med Biol Res 2005; 38:361-5; PMID:15761615; http://dx.doi.org/10.1590/S0100-879X2005000300006
110. Nosho K, Yamamoto H, Mikami M, Taniguchi H, Takahashi T, Adachi Y, Imamura A, Imai K, Shinomura Y. Overexpression of poly(ADP-ribose) polymerase-1 (PARP-1) in the early stage of colorectal carcinogenesis. Eur J Cancer 2006; 42:2374-81; PMID:16809031; http://dx.doi.org/10.1016/j.ejca.2006.01.061
111. Idogawa M, Masutani M, Shitashige M, Honda K, Tokino T, Shinomura Y, Imai K, Hirohashi S, Yamada T. Ku70 and poly(ADP-ribose) polymerase-1 competitively regulate β-catenin and T-cell factor-4-mediated gene transactivation: possible linkage of DNA damage recognition and Wnt signaling. Cancer Res 2007; 67:911-8; PMID:17283121; http://dx.doi.org/10.1158/0008-5472.CAN-06-2360
112. Idogawa M, Yamada T, Honda K, Sato S, Imai K, Hirohashi S. Poly(ADP-ribose) polymerase-1 is a component of the oncogenic T-cell factor-4/β-catenin complex. Gastroenterology 2005; 128:1919-36; PMID:15940627; http://dx.doi.org/10.1053/j.gastro.2005.03.007
113. Postawski K, Monist M, Keith G. PARP-1 activity in normal and cancerous human endometrium and its relationship with quantity of abasic sites (AP). Ginekol Pol 2011; 82:16-21; PMID:21469519
114. Nomura F, Yaguchi M, Togawa A, Miyazaki M, Isobe K, Miyake M, Noda M, Nakai T. Enhancement of poly-adenosine diphosphate-ribosylation in human hepatocellular carcinoma. J Gastroenterol Hepatol 2000; 15:529-35; PMID:10847440; http://dx.doi.org/10.1046/j.1440-1746.2000.02193.x
115. Byers LA, Wang J, Nilsson MB, Fujimoto J, Saintigny P, Yordy J, Giri U, Peyton M, Fan YH, Diao L, et al. Proteomic profiling identifies dysregulated pathways in small cell lung cancer and novel therapeutic targets including PARP1. Cancer Discov 2012; 2:798-811; PMID:22961666; http://dx.doi.org/10.1158/2159-8290.CD-12-0112
116. Brustmann H. Poly(adenosine diphosphate-ribose) polymerase expression in serous ovarian carcinoma: correlation with p53, MIB-1, and outcome. Int J Gynecol Pathol 2007; 26:147-53; PMID:17413981; http://dx.doi.org/10.1097/pgp.0b013e3180555999
117. Gan A, Green AR, Nolan CC, Martin S, Deen S. Poly(adenosine diphosphate-ribose) polymerase expression in BRCA-proficient ovarian high-grade serous carcinoma; association with patient survival. Hum Pathol 2013; 44:1638-47; PMID:23574784; http://dx.doi.org/10.1016/j.humpath.2013.01.015
118. Bi FF, Li D, Yang Q. Promoter hypomethylation, especially around the E26 transformation-specific motif, and increased expression of poly (ADP-ribose) polymerase 1 in BRCA-mutated serous ovarian cancer. BMC Cancer 2013; 13:90; PMID:23442605; http://dx.doi.org/10.1186/1471-2407-13-90
119. Wu W, Zhu H, Liang Y, Kong Z, Duan X, Li S, Zhao Z, Yang D, Zeng G. Expression of PARP-1 and its active polymer PAR in prostate cancer and benign prostatic hyperplasia in Chinese patients. Int Urol Nephrol 2014; 46:1345-9; PMID:24436031; http://dx.doi.org/10.1007/s11255-014-0642-0
120. Salemi M, Galia A, Fraggetta F, La Corte C, Pepe P, La Vignera S, Improta G, Bosco P, Calogero AE. Poly (ADP-ribose) polymerase 1 protein expression in normal and neoplastic prostatic tissue. Eur J Histochem 2013; 57:e13; PMID:23807292; http://dx.doi.org/10.4081/ejh.2013.e13
121. McNealy T, Frey M, Trojan L, Knoll T, Alken P, Michel MS. Intrinsic presence of poly (ADP-ribose) is significantly increased in malignant prostate compared to benign prostate cell lines. Anticancer Res 2003; 23:1473-8; PMID:12820412
122. Staibano S, Pepe S, Lo Muzio L, Somma P, Mascolo M, Argenziano G, Scalvenzi M, Salvatore G, Fabbrocini G, Molea G, et al. Poly(adenosine diphosphate-ribose) polymerase 1 expression in malignant melanomas from photoexposed areas of the head and neck region. Hum Pathol 2005; 36:724-31; PMID:16084940; http://dx.doi.org/10.1016/j.humpath.2005.04.017
123. Tentori L, Muzi A, Dorio AS, Bultrini S, Mazzon E, Lacal PM, Shah GM, Zhang J, Navarra P, Nocentini G, et al. Stable depletion of poly (ADP-ribose) polymerase-1 reduces in vivo melanoma growth and increases chemosensitivity. Eur J Cancer 2008; 44:1302-14; PMID:18440222; http://dx.doi.org/10.1016/j.ejca.2008.03.019
124. Newman RE, Soldatenkov VA, Dritschilo A, Notario V. Poly(ADP-ribose) polymerase turnover alterations do not contribute to PARP overexpression in Ewing's sarcoma cells. Oncol Rep 2002; 9:529-32; PMID:11956622
125. Prasad SC, Thraves PJ, Bhatia KG, Smulson ME, Dritschilo A. Enhanced poly(adenosine diphosphate ribose) polymerase activity and gene expression in Ewing's sarcoma cells. Cancer Res 1990; 50:38-43; PMID:2104538
126. Galia A, Calogero AE, Condorelli R, Fraggetta F, La Corte A, Ridolfo F, Bosco P, Castiglione R, Salemi M. PARP-1 protein expression in glioblastoma multiforme. Eur J Histochem 2012; 56:e9; PMID:22472897; http://dx.doi.org/10.4081/ejh.2012.e9
127. Wharton SB, McNelis U, Bell HS, Whittle IR. Expression of poly(ADP-ribose) polymerase and distribution of poly(ADP-ribosyl)ation in glioblastoma and in a glioma multicellular tumour spheroid model. Neuropathol Appl Neurobiol 2000; 26:528-35; PMID:11123719; http://dx.doi.org/10.1046/j.0305-1846.2000.00288.x
128. Csonka T, Murnyak B, Szepesi R, Kurucz A, Klekner A, Hortobagyi T. Poly(ADP-ribose) polymerase-1 (PARP1) and p53 labelling index correlates with tumour grade in meningiomas. Folia Neuropathol 2014; 52:111-20; PMID:25118896; http://dx.doi.org/10.5114/fn.2014.43782
129. Rajaee-Behbahani N, Schmezer P, Ramroth H, Burkle A, Bartsch H, Dietz A, Becher H. Reduced poly(ADP-ribosyl)ation in lymphocytes of laryngeal cancer patients: results of a case-control study. Int J Cancer 2002; 98:780-4; PMID:11920651; http://dx.doi.org/10.1002/ijc.10234
130. von Minckwitz G, Muller BM, Loibl S, Budczies J, Hanusch C, Darb-Esfahani S, Hilfrich J, Weiss E, Huober J, Blohmer JU, et al. Cytoplasmic poly(adenosine diphosphate-ribose) polymerase expression is predictive and prognostic in patients with breast cancer treated with neoadjuvant chemotherapy. J Clin Oncol 2011; 29:2150-7; PMID:21519019; http://dx.doi.org/10.1200/JCO.2010.31.9079
131. Nobori T, Yamanaka H, Carson DA. Poly(ADP-ribose) polymerase inhibits DNA synthesis initiation in the absence of NAD. Biochem Biophys Res Commun 1989; 163:1113-8; PMID:2506850; http://dx.doi.org/10.1016/0006-291X(89)92336-X
132. Menear KA, Adcock C, Boulter R, Cockcroft XL, Copsey L, Cranston A, Dillon KJ, Drzewiecki J, Garman S, Gomez S, et al. Four-; [3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin- 1-one: a novel bioavailable inhibitor of poly(ADP-ribose) polymerase-1. J Med Chem 2008; 51:6581-91; PMID:18800822; http://dx.doi.org/10.1021/jm8001263
133. Thomas HD, Calabrese CR, Batey MA, Canan S, Hostomsky Z, Kyle S, Maegley KA, Newell DR, Skalitzky D, Wang LZ, et al. Preclinical selection of a novel poly(ADP-ribose) polymerase inhibitor for clinical trial. Mol Cancer Ther 2007; 6:945-56; PMID:17363489; http://dx.doi.org/10.1158/1535-7163.MCT-06-0552
134. Donawho CK, Luo Y, Luo Y, Penning TD, Bauch JL, Bouska JJ, Bontcheva-Diaz VD, Cox BF, DeWeese TL, Dillehay LE, et al. ABT-888, an orally active poly(ADP-ribose) polymerase inhibitor that potentiates DNA-damaging agents in preclinical tumor models. Clin Cancer Res 2007; 13:2728-37; PMID:17473206; http://dx.doi.org/10.1158/1078-0432.CCR-06-3039
135. Jones P, Altamura S, Boueres J, Ferrigno F, Fonsi M, Giomini C, Lamartina S, Monteagudo E, Ontoria JM, Orsale MV, et al. Discovery of 2-{4-; [(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide (MK-4827): a novel oral poly(ADP-ribose)polymerase (PARP) inhibitor efficacious in BRCA-1 and -2 mutant tumors. J Med Chem 2009; 52:7170-85; PMID:19873981; http://dx.doi.org/10.1021/jm901188v
136. Chuang HC, Kapuriya N, Kulp SK, Chen CS, Shapiro CL. Differential anti-proliferative activities of poly(ADP-ribose) polymerase (PARP) inhibitors in triple-negative breast cancer cells. Breast Cancer Res Treat 2012; 134:649-59; PMID:22678161; http://dx.doi.org/10.1007/s10549-012-2106-5
137. Patel AG, De Lorenzo SB, Flatten KS, Poirier GG, Kaufmann SH. Failure of iniparib to inhibit poly(ADP-Ribose) polymerase in vitro. Clin Cancer Res 2012; 18:1655-62; PMID:22291137; http://dx.doi.org/10.1158/1078-0432.CCR-11-2890
138. Mendeleyev J, Kirsten E, Hakam A, Buki KG, Kun E. Potential chemotherapeutic activity of 4-iodo-3-nitrobenzamide. Metabolic reduction to the 3-nitroso derivative and induction of cell death in tumor cells in culture. Biochem Pharmacol 1995; 50:705-14; PMID:7669074; http://dx.doi.org/10.1016/0006-2952(95)00189-7
139. Miknyoczki S, Chang H, Grobelny J, Pritchard S, Worrell C, McGann N, Ator M, Husten J, Deibold J, Hudkins R, et al. The selective poly(ADP-ribose) polymerase-1(2) inhibitor, CEP-8983, increases the sensitivity of chemoresistant tumor cells to temozolomide and irinotecan but does not potentiate myelotoxicity. Mol Cancer Ther 2007; 6:2290-302; PMID:17699724; http://dx.doi.org/10.1158/1535-7163.MCT-07-0062
140. Russo AL, Kwon HC, Burgan WE, Carter D, Beam K, Weizheng X, Zhang J, Slusher BS, Chakravarti A, Tofilon PJ, et al. In vitro and in vivo radiosensitization of glioblastoma cells by the poly (ADP-ribose) polymerase inhibitor E7016. Clin Cancer Res 2009; 15:607-12; PMID:19147766; http://dx.doi.org/10.1158/1078-0432.CCR-08-2079
141. Brock WA, Milas L, Bergh S, Lo R, Szabo C, Mason KA. Radiosensitization of human and rodent cell lines by INO-1001, a novel inhibitor of poly(ADP-ribose) polymerase. Cancer Lett 2004; 205:155-60; PMID:15036647; http://dx.doi.org/10.1016/j.canlet.2003.10.029
142. Michels J, Vitale I, Saparbaev M, Castedo M, Kroemer G. Predictive biomarkers for cancer therapy with PARP inhibitors. Oncogene 2014; 33:3894-907; PMID:24037533; http://dx.doi.org/10.1038/onc.2013.352
143. Michels J, Obrist F, Castedo M, Vitale I, Kroemer G. PARP and other prospective targets for poisoning cancer cell metabolism. Biochem Pharmacol 2014; 92:164-71; PMID:25199458; http://dx.doi.org/10.1016/j.bcp.2014.08.026
144. Curtin NJ, Szabo C. Therapeutic applications of PARP inhibitors: anticancer therapy and beyond. Mol Aspects Med 2013; 34:1217-56; PMID:23370117; http://dx.doi.org/10.1016/j.mam.2013.01.006
145. Wahlberg E, Karlberg T, Kouznetsova E, Markova N, Macchiarulo A, Thorsell AG, Pol E, Frostell A, Ekblad T, Oncu D, et al. Family-wide chemical profiling and structural analysis of PARP and tankyrase inhibitors. Nat Biotechnol 2012; 30:283-8; PMID:22343925; http://dx.doi.org/10.1038/nbt.2121
146. Kummar S, Chen A, Parchment RE, Kinders RJ, Ji J, Tomaszewski JE, Doroshow JH. Advances in using PARP inhibitors to treat cancer. BMC Med 2012; 10:25; PMID:22401667; http://dx.doi.org/10.1186/1741-7015-10-25
147. Leung M, Rosen D, Fields S, Cesano A, Budman DR. Poly(ADP-ribose) polymerase-1 inhibition: preclinical and clinical development of synthetic lethality. Mol Med 2011; 17:854-62; PMID:21424107; http://dx.doi.org/10.2119/molmed.2010.00240
148. Zaremba T, Curtin NJ. PARP inhibitor development for systemic cancer targeting. Anticancer Agents Med Chem 2007; 7:515-23; PMID:17896912; http://dx.doi.org/10.2174/187152007781668715
149. Ratnam K, Low JA. Current development of clinical inhibitors of poly(ADP-ribose) polymerase in oncology. Clin Cancer Res 2007; 13:1383-8; PMID:17332279; http://dx.doi.org/10.1158/1078-0432.CCR-06-2260
150. Dobzhansky T. Genetics of natural populations. Xiii. recombination and variability in populations of drosophila pseudoobscura. Genetics 1946; 31:269-90; PMID:17247197
151. Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, Santarosa M, Dillon KJ, Hickson I, Knights C, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 2005; 434:917-21; PMID:15829967; http://dx.doi.org/10.1038/nature03445
152. Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, Kyle S, Meuth M, Curtin NJ, Helleday T. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 2005; 434:913-7; PMID:15829966; http://dx.doi.org/10.1038/nature03443
153. Lee JM, Ledermann JA, Kohn EC. PARP Inhibitors for BRCA1/2 mutation-associated and BRCA-like malignancies. Ann Oncol 2014; 25:32-40; PMID:24225019; http://dx.doi.org/10.1093/annonc/mdt384
154. Turner N, Tutt A, Ashworth A. Hallmarks of ‘BRCAness’ in sporadic cancers. Nat Rev Cancer 2004; 4:814-9; PMID:15510162; http://dx.doi.org/10.1038/nrc1457
155. McCabe N, Turner NC, Lord CJ, Kluzek K, Bialkowska A, Swift S, Giavara S, O'Connor MJ, Tutt AN, Zdzienicka MZ, et al. Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition. Cancer Res 2006; 66:8109-15; PMID:16912188; http://dx.doi.org/10.1158/0008-5472.CAN-06-0140
156. Williamson CT, Muzik H, Turhan AG, Zamo A, O'Connor MJ, Bebb DG, Lees-Miller SP. ATM deficiency sensitizes mantle cell lymphoma cells to poly(ADP-ribose) polymerase-1 inhibitors. Mol Cancer Ther 2010; 9:347-57; PMID:20124459; http://dx.doi.org/10.1158/1535-7163.MCT-09-0872
157. Williamson CT, Kubota E, Hamill JD, Klimowicz A, Ye R, Muzik H, Dean M, Tu L, Gilley D, Magliocco AM, et al. Enhanced cytotoxicity of PARP inhibition in mantle cell lymphoma harbouring mutations in both ATM and p53. EMBO Mol Med 2012; 4:515-27; PMID:22416035; http://dx.doi.org/10.1002/emmm.201200229
158. Huehls AM, Wagner JM, Huntoon CJ, Karnitz LM. Identification of DNA repair pathways that affect the survival of ovarian cancer cells treated with a poly(ADP-ribose) polymerase inhibitor in a novel drug combination. Mol Pharmacol 2012; 82:767-76; PMID:22833573; http://dx.doi.org/10.1124/mol.112.080614
159. Weston VJ, Oldreive CE, Skowronska A, Oscier DG, Pratt G, Dyer MJ, Smith G, Powell JE, Rudzki Z, Kearns P, et al. The PARP inhibitor olaparib induces significant killing of ATM-deficient lymphoid tumor cells in vitro and in vivo. Blood 2010; 116:4578-87; PMID:20739657; http://dx.doi.org/10.1182/blood-2010-01-265769
160. Gilardini Montani MS, Prodosmo A, Stagni V, Merli D, Monteonofrio L, Gatti V, Gentileschi MP, Barila D, Soddu S. ATM-depletion in breast cancer cells confers sensitivity to PARP inhibition. J Exp Clin Cancer Res 2013; 32:95; PMID:24252502; http://dx.doi.org/10.1186/1756-9966-32-95
161. Huntoon CJ, Flatten KS, Wahner Hendrickson AE, Huehls AM, Sutor SL, Kaufmann SH, Karnitz LM. ATR inhibition broadly sensitizes ovarian cancer cells to chemotherapy independent of BRCA status. Cancer Res 2013; 73:3683-91; PMID:23548269; http://dx.doi.org/10.1158/0008-5472.CAN-13-0110
162. Iorns E, Lord CJ, Turner N, Ashworth A. Utilizing RNA interference to enhance cancer drug discovery. Nat Rev Drug Discov 2007; 6:556-68; PMID:17599085; http://dx.doi.org/10.1038/nrd2355
163. Taniguchi T, Tischkowitz M, Ameziane N, Hodgson SV, Mathew CG, Joenje H, Mok SC, D'Andrea AD. Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors. Nat Med 2003; 9:568-74; PMID:12692539; http://dx.doi.org/10.1038/nm852
164. Renwick A, Thompson D, Seal S, Kelly P, Chagtai T, Ahmed M, North B, Jayatilake H, Barfoot R, Spanova K, et al. ATM mutations that cause ataxia-telangiectasia are breast cancer susceptibility alleles. Nat Genet 2006; 38:873-5; PMID:16832357; http://dx.doi.org/10.1038/ng1837
165. Boultwood J. Ataxia telangiectasia gene mutations in leukaemia and lymphoma. J Clin Pathol 2001; 54:512-6; PMID:11429421; http://dx.doi.org/10.1136/jcp.54.7.512
166. Nevanlinna H, Bartek J. The CHEK2 gene and inherited breast cancer susceptibility. Oncogene 2006; 25:5912-9; PMID:16998506; http://dx.doi.org/10.1038/sj.onc.1209877
167. Mendes-Pereira AM, Martin SA, Brough R, McCarthy A, Taylor JR, Kim JS, Waldman T, Lord CJ, Ashworth A. Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors. EMBO Mol Med 2009; 1:315-22; PMID:20049735; http://dx.doi.org/10.1002/emmm.200900041
168. Dedes KJ, Wetterskog D, Mendes-Pereira AM, Natrajan R, Lambros MB, Geyer FC, Vatcheva R, Savage K, Mackay A, Lord CJ, et al. PTEN deficiency in endometrioid endometrial adenocarcinomas predicts sensitivity to PARP inhibitors. Sci Transl Med 2010; 2:53ra75; PMID:20944090; http://dx.doi.org/10.1126/scitranslmed.3001538
169. McEllin B, Camacho CV, Mukherjee B, Hahm B, Tomimatsu N, Bachoo RM, Burma S. PTEN loss compromises homologous recombination repair in astrocytes: implications for glioblastoma therapy with temozolomide or poly(ADP-ribose) polymerase inhibitors. Cancer Res 2010; 70:5457-64; PMID:20530668; http://dx.doi.org/10.1158/0008-5472.CAN-09-4295
170. Minami D, Takigawa N, Takeda H, Takata M, Ochi N, Ichihara E, Hisamoto A, Hotta K, Tanimoto M, Kiura K. Synergistic effect of olaparib with combination of cisplatin on PTEN-deficient lung cancer cells. Mol Cancer Res 2013; 11:140-8; PMID:23239809; http://dx.doi.org/10.1158/1541-7786.MCR-12-0401
171. Chatterjee P, Choudhary GS, Sharma A, Singh K, Heston WD, Ciezki J, Klein EA, Almasan A. PARP inhibition sensitizes to low dose-rate radiation TMPRSS2-ERG fusion gene-expressing and PTEN-deficient prostate cancer cells. PLoS One 2013; 8:e60408; PMID:23565244
172. Vilar E, Bartnik CM, Stenzel SL, Raskin L, Ahn J, Moreno V, Mukherjee B, Iniesta MD, Morgan MA, Rennert G, et al. MRE11 deficiency increases sensitivity to poly(ADP-ribose) polymerase inhibition in microsatellite unstable colorectal cancers. Cancer Res 2011; 71:2632-42; PMID:21300766; http://dx.doi.org/10.1158/0008-5472.CAN-10-1120
173. McPherson LA, Shen Y, Ford JM. Poly (ADP-ribose) polymerase inhibitor LT-626: Sensitivity correlates with MRE11 mutations and synergizes with platinums and irinotecan in colorectal cancer cells. Cancer Lett 2014; 343:217-23; PMID:24215868; http://dx.doi.org/10.1016/j.canlet.2013.10.034
174. Gaymes TJ, Mohamedali AM, Patterson M, Matto N, Smith A, Kulasekararaj A, Chelliah R, Curtin N, Farzaneh F, Shall S, et al. Microsatellite instability induced mutations in DNA repair genes CtIP and MRE11 confer hypersensitivity to poly (ADP-ribose) polymerase inhibitors in myeloid malignancies. Haematologica 2013; 98:1397-406; PMID:23349304; http://dx.doi.org/10.3324/haematol.2012.079251
175. Metzger-Filho O, Tutt A, de Azambuja E, Saini KS, Viale G, Loi S, Bradbury I, Bliss JM, Azim HA, Jr., Ellis P, et al. Dissecting the heterogeneity of triple-negative breast cancer. J Clin Oncol 2012; 30:1879-87; PMID:22454417; http://dx.doi.org/10.1200/JCO.2011.38.2010
176. Jacot W, Thezenas S, Senal R, Viglianti C, Laberenne AC, Lopez-Crapez E, Bibeau F, Bleuse JP, Romieu G, Lamy PJ. BRCA1 promoter hypermethylation, 53BP1 protein expression and PARP-1 activity as biomarkers of DNA repair deficit in breast cancer. BMC Cancer 2013; 13:523; PMID:24191908; http://dx.doi.org/10.1186/1471-2407-13-523
177. Lips EH, Mulder L, Oonk A, van der Kolk LE, Hogervorst FB, Imholz AL, Wesseling J, Rodenhuis S, Nederlof PM. Triple-negative breast cancer: BRCAness and concordance of clinical features with BRCA1-mutation carriers. Br J Cancer 2013; 108:2172-7; PMID:23558900; http://dx.doi.org/10.1038/bjc.2013.144
178. Hartman AR, Kaldate RR, Sailer LM, Painter L, Grier CE, Endsley RR, Griffin M, Hamilton SA, Frye CA, Silberman MA, et al. Prevalence of BRCA mutations in an unselected population of triple-negative breast cancer. Cancer 2012; 118:2787-95; PMID:22614657; http://dx.doi.org/10.1002/cncr.26576
179. Gonzalez-Angulo AM, Timms KM, Liu S, Chen H, Litton JK, Potter J, Lanchbury JS, Stemke-Hale K, Hennessy BT, Arun BK, et al. Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer. Clin Cancer Res 2011; 17:1082-9; PMID:21233401; http://dx.doi.org/10.1158/1078-0432.CCR-10-2560
180. Anders CK, Winer EP, Ford JM, Dent R, Silver DP, Sledge GW, Carey LA. Poly(ADP-Ribose) polymerase inhibition: “targeted” therapy for triple-negative breast cancer. Clin Cancer Res 2010; 16:4702-10; PMID:20858840; http://dx.doi.org/10.1158/1078-0432.CCR-10-0939
181. Alli E, Sharma VB, Sunderesakumar P, Ford JM. Defective repair of oxidative dna damage in triple-negative breast cancer confers sensitivity to inhibition of poly(ADP-ribose) polymerase. Cancer Res 2009; 69:3589-96; PMID:19351835; http://dx.doi.org/10.1158/0008-5472.CAN-08-4016
182. Ceccaldi R, Liu JC, Amunugama R, Hajdu I, Primack B, Petalcorin MI, O'Connor KW, Konstantinopoulos PA, Elledge SJ, Boulton SJ, et al. Homologous-recombination-deficient tumours are dependent on Poltheta-mediated repair. Nature 2015; 518:258-62; PMID:25642963; http://dx.doi.org/10.1038/nature14184
183. Mateos-Gomez PA, Gong F, Nair N, Miller KM, Lazzerini-Denchi E, Sfeir A. Mammalian polymerase theta promotes alternative NHEJ and suppresses recombination. Nature 2015; 518:254-7; PMID:25642960; http://dx.doi.org/10.1038/nature14157
184. Ibrahim YH, Garcia-Garcia C, Serra V, He L, Torres-Lockhart K, Prat A, Anton P, Cozar P, Guzman M, Grueso J, et al. PI3K inhibition impairs BRCA1/2 expression and sensitizes BRCA-proficient triple-negative breast cancer to PARP inhibition. Cancer Discov 2012; 2:1036-47; PMID:22915752; http://dx.doi.org/10.1158/2159-8290.CD-11-0348
185. Juvekar A, Burga LN, Hu H, Lunsford EP, Ibrahim YH, Balmana J, Rajendran A, Papa A, Spencer K, Lyssiotis CA, et al. Combining a PI3K inhibitor with a PARP inhibitor provides an effective therapy for BRCA1-related breast cancer. Cancer Discov 2012; 2:1048-63; PMID:22915751; http://dx.doi.org/10.1158/2159-8290.CD-11-0336
186. De P, Sun Y, Carlson JH, Friedman LS, Leyland-Jones BR, Dey N. Doubling down on the PI3K-AKT-mTOR pathway enhances the antitumor efficacy of PARP inhibitor in triple negative breast cancer model beyond BRCA-ness. Neoplasia 2014; 16:43-72; PMID:24563619; http://dx.doi.org/10.1593/neo.131694
187. Johnson N, Li YC, Walton ZE, Cheng KA, Li D, Rodig SJ, Moreau LA, Unitt C, Bronson RT, Thomas HD, et al. Compromised CDK1 activity sensitizes BRCA-proficient cancers to PARP inhibition. Nat Med 2011; 17:875-82; PMID:21706030; http://dx.doi.org/10.1038/nm.2377
188. To C, Kim EH, Royce DB, Williams CR, Collins RM, Risingsong R, Sporn MB, Liby KT. The PARP inhibitors, veliparib and olaparib, are effective chemopreventive agents for delaying mammary tumor development in BRCA1-deficient mice. Cancer Prev Res (Phila) 2014; 7:698-707; PMID:24817481; http://dx.doi.org/10.1158/1940-6207.CAPR-14-0047
189. Gottipati P, Vischioni B, Schultz N, Solomons J, Bryant HE, Djureinovic T, Issaeva N, Sleeth K, Sharma RA, Helleday T. Poly(ADP-ribose) polymerase is hyperactivated in homologous recombination-defective cells. Cancer Res 2010; 70:5389-98; PMID:20551068; http://dx.doi.org/10.1158/0008-5472.CAN-09-4716
190. Michels J, Vitale I, Galluzzi L, Adam J, Olaussen KA, Kepp O, Senovilla L, Talhaoui I, Guegan J, Enot DP, et al. Cisplatin resistance associated with PARP hyperactivation. Cancer Res 2013; 73:2271-80; PMID:23554447; http://dx.doi.org/10.1158/0008-5472.CAN-12-3000
191. Nowsheen S, Bonner JA, Yang ES. The poly(ADP-Ribose) polymerase inhibitor ABT-888 reduces radiation-induced nuclear EGFR and augments head and neck tumor response to radiotherapy. Radiother Oncol 2011; 99:331-8; PMID:21719137; http://dx.doi.org/10.1016/j.radonc.2011.05.084
192. Shall S, de Murcia G. Poly(ADP-ribose) polymerase-1: what have we learned from the deficient mouse model? Mutat Res 2000; 460:1-15; PMID:10856830; http://dx.doi.org/10.1016/S0921-8777(00)00016-1
193. Patel AG, Sarkaria JN, Kaufmann SH. Nonhomologous end joining drives poly(ADP-ribose) polymerase (PARP) inhibitor lethality in homologous recombination-deficient cells. Proc Natl Acad Sci U S A 2011; 108:3406-11; PMID:21300883; http://dx.doi.org/10.1073/pnas.1013715108
194. Bouwman P, Aly A, Escandell JM, Pieterse M, Bartkova J, van der Gulden H, Hiddingh S, Thanasoula M, Kulkarni A, Yang Q, et al. 53BP1 loss rescues BRCA1 deficiency and is associated with triple-negative and BRCA-mutated breast cancers. Nat Struct Mol Biol 2010; 17:688-95; PMID:20453858; http://dx.doi.org/10.1038/nsmb.1831
195. Murai J, Huang SY, Das BB, Renaud A, Zhang Y, Doroshow JH, Ji J, Takeda S, Pommier Y. Trapping of PARP1 and PARP2 by Clinical PARP Inhibitors. Cancer Res 2012; 72:5588-99; PMID:23118055; http://dx.doi.org/10.1158/0008-5472.CAN-12-2753
196. Helleday T. The underlying mechanism for the PARP and BRCA synthetic lethality: clearing up the misunderstandings. Mol Oncol 2011; 5:387-93; PMID:21821475; http://dx.doi.org/10.1016/j.molonc.2011.07.001
197. Shen Y, Aoyagi-Scharber M, Wang B. Trapping Poly(ADP-Ribose) Polymerase. J Pharmacol Exp Ther 2015; 353:446-57; PMID:25758918; http://dx.doi.org/10.1124/jpet.114.222448
198. Murai J, Zhang Y, Morris J, Ji J, Takeda S, Doroshow JH, Pommier Y. Rationale for poly(ADP-ribose) polymerase (PARP) inhibitors in combination therapy with camptothecins or temozolomide based on PARP trapping vs. catalytic inhibition. J Pharmacol Exp Ther 2014; 349:408-16; PMID:24650937; http://dx.doi.org/10.1124/jpet.113.210146
199. Murai J, Huang SY, Renaud A, Zhang Y, Ji J, Takeda S, Morris J, Teicher B, Doroshow JH, Pommier Y. Stereospecific PARP trapping by BMN 673 and comparison with olaparib and rucaparib. Mol Cancer Ther 2014; 13:433-43; PMID:24356813; http://dx.doi.org/10.1158/1535-7163.MCT-13-0803
200. Anders C, Deal AM, Abramson V, Liu MC, Storniolo AM, Carpenter JT, Puhalla S, Nanda R, Melhem-Bertrandt A, Lin NU, et al. TBCRC 018: phase II study of iniparib in combination with irinotecan to treat progressive triple negative breast cancer brain metastases. Breast Cancer Res Treat 2014; 146:557-66; PMID:25001612; http://dx.doi.org/10.1007/s10549-014-3039-y
201. Aghajanian C, Sill MW, Secord AA, Powell MA, Steinhoff M. Iniparib plus paclitaxel and carboplatin as initial treatment of advanced or recurrent uterine carcinosarcoma: a Gynecologic Oncology Group Study. Gynecol Oncol 2012; 126:424-7; PMID:22634397; http://dx.doi.org/10.1016/j.ygyno.2012.05.024
202. Novello S, Besse B, Felip E, Barlesi F, Mazieres J, Zalcman G, von Pawel J, Reck M, Cappuzzo F, Ferry D, et al. A phase II randomized study evaluating the addition of iniparib to gemcitabine plus cisplatin as first-line therapy for metastatic non-small-cell lung cancer. Ann Oncol 2014; 25:2156-62; PMID:25139550; http://dx.doi.org/10.1093/annonc/mdu384
203. O'Shaughnessy J, Osborne C, Pippen JE, Yoffe M, Patt D, Rocha C, Koo IC, Sherman BM, Bradley C. Iniparib plus chemotherapy in metastatic triple-negative breast cancer. N Engl J Med 2011; 364:205-14; PMID:21208101; http://dx.doi.org/10.1056/NEJMoa1011418
204. O'Shaughnessy J, Schwartzberg L, Danso MA, Miller KD, Rugo HS, Neubauer M, Robert N, Hellerstedt B, Saleh M, Richards P, et al. Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer. J Clin Oncol 2014; 32:3840-7; PMID:25349301; http://dx.doi.org/10.1200/JCO.2014.55.2984
205. Kaufman B, Shapira-Frommer R, Schmutzler RK, Audeh MW, Friedlander M, Balmana J, Mitchell G, Fried G, Stemmer SM, Hubert A, et al. Olaparib monotherapy in patients with advanced cancer and a germline BRCA1/2 mutation. J Clin Oncol 2015; 33:244-50; PMID:25366685; http://dx.doi.org/10.1200/JCO.2014.56.2728
206. Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M, Mortimer P, Swaisland H, Lau A, O'Connor MJ, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N Engl J Med 2009; 361:123-34; PMID:19553641; http://dx.doi.org/10.1056/NEJMoa0900212
207. Yamamoto N, Nokihara H, Yamada Y, Goto Y, Tanioka M, Shibata T, Yamada K, Asahina H, Kawata T, Shi X, et al. A Phase I, dose-finding and pharmacokinetic study of olaparib (AZD2281) in Japanese patients with advanced solid tumors. Cancer Sci 2012; 103:504-9; PMID:22145984; http://dx.doi.org/10.1111/j.1349-7006.2011.02179.x
208. Del Conte G, Sessa C, von Moos R, Vigano L, Digena T, Locatelli A, Gallerani E, Fasolo A, Tessari A, Cathomas R, et al. Phase I study of olaparib in combination with liposomal doxorubicin in patients with advanced solid tumours. Br J Cancer 2014; 111:651-9; PMID:25025963; http://dx.doi.org/10.1038/bjc.2014.345
209. Fong PC, Yap TA, Boss DS, Carden CP, Mergui-Roelvink M, Gourley C, De Greve J, Lubinski J, Shanley S, Messiou C, et al. Poly(ADP)-ribose polymerase inhibition: frequent durable responses in BRCA carrier ovarian cancer correlating with platinum-free interval. J Clin Oncol 2010; 28:2512-9; PMID:20406929; http://dx.doi.org/10.1200/JCO.2009.26.9589
210. Bundred N, Gardovskis J, Jaskiewicz J, Eglitis J, Paramonov V, McCormack P, Swaisland H, Cavallin M, Parry T, Carmichael J, et al. Evaluation of the pharmacodynamics and pharmacokinetics of the PARP inhibitor olaparib: a phase I multicentre trial in patients scheduled for elective breast cancer surgery. Invest New Drugs 2013; 31:949-58; PMID:23315029; http://dx.doi.org/10.1007/s10637-012-9922-7
211. Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, Friedlander M, Arun B, Loman N, Schmutzler RK, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet 2010; 376:235-44; PMID:20609467; http://dx.doi.org/10.1016/S0140-6736(10)60892-6
212. Kaye SB, Lubinski J, Matulonis U, Ang JE, Gourley C, Karlan BY, Amnon A, Bell-McGuinn KM, Chen LM, Friedlander M, et al. Phase II, open-label, randomized, multicenter study comparing the efficacy and safety of olaparib, a poly (ADP-ribose) polymerase inhibitor, and pegylated liposomal doxorubicin in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer. J Clin Oncol 2012; 30:372-9; PMID:22203755; http://dx.doi.org/10.1200/JCO.2011.36.9215
213. Audeh MW, Carmichael J, Penson RT, Friedlander M, Powell B, Bell-McGuinn KM, Scott C, Weitzel JN, Oaknin A, Loman N, et al. Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and recurrent ovarian cancer: a proof-of-concept trial. Lancet 2010; 376:245-51; PMID:20609468; http://dx.doi.org/10.1016/S0140-6736(10)60893-8
214. Gelmon KA, Tischkowitz M, Mackay H, Swenerton K, Robidoux A, Tonkin K, Hirte H, Huntsman D, Clemons M, Gilks B, et al. Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study. Lancet Oncol 2011; 12:852-61; PMID:21862407; http://dx.doi.org/10.1016/S1470-2045(11)70214-5
215. Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott C, Meier W, Shapira-Frommer R, Safra T, et al. Olaparib maintenance therapy in platinum-sensitive relapsed ovarian cancer. N Engl J Med 2012; 366:1382-92; PMID:22452356; http://dx.doi.org/10.1056/NEJMoa1105535
216. Choy E, Butrynski JE, Harmon DC, Morgan JA, George S, Wagner AJ, D'Adamo D, Cote GM, Flamand Y, Benes CH, et al. Phase II study of olaparib in patients with refractory Ewing sarcoma following failure of standard chemotherapy. BMC Cancer 2014; 14:813; PMID:25374341; http://dx.doi.org/10.1186/1471-2407-14-813
217. Sandhu SK, Schelman WR, Wilding G, Moreno V, Baird RD, Miranda S, Hylands L, Riisnaes R, Forster M, Omlin A, et al. The poly(ADP-ribose) polymerase inhibitor niraparib (MK4827) in BRCA mutation carriers and patients with sporadic cancer: a phase 1 dose-escalation trial. Lancet Oncol 2013; 14:882-92; PMID:23810788; http://dx.doi.org/10.1016/S1470-2045(13)70240-7
218. Coleman RL, Sill MW, Bell-McGuinn K, Aghajanian C, Gray HJ, Tewari KS, Rubin SC, Rutherford TJ, Chan JK, Chen A, et al. A phase II evaluation of the potent, highly selective PARP inhibitor veliparib in the treatment of persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer in patients who carry a germline BRCA1 or BRCA2 mutation–An NRG Oncology/Gynecologic Oncology Group study. Gynecol Oncol 2015; 137:386-91; PMID:25818403; doi: 10.1016/j.ygyno.2015.03.042
219. Ledermann J, Harter P, Gourley C, Friedlander M, Vergote I, Rustin G, Scott CL, Meier W, Shapira-Frommer R, Safra T, et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol 2014; 15:852-61; PMID:24882434; http://dx.doi.org/10.1016/S1470-2045(14)70228-1
220. Eggermont AM, Kirkwood JM. Re-evaluating the role of dacarbazine in metastatic melanoma: what have we learned in 30 years? Eur J Cancer 2004; 40:1825-36; PMID:15288283; http://dx.doi.org/10.1016/j.ejca.2004.04.030
221. Khan OA, Gore M, Lorigan P, Stone J, Greystoke A, Burke W, Carmichael J, Watson AJ, McGown G, Thorncroft M, et al. A phase I study of the safety and tolerability of olaparib (AZD2281, KU0059436) and dacarbazine in patients with advanced solid tumours. Br J Cancer 2011; 104:750-5; PMID:21326243; http://dx.doi.org/10.1038/bjc.2011.8
222. Galluzzi L, Vitale I, Senovilla L, Olaussen KA, Pinna G, Eisenberg T, Goubar A, Martins I, Michels J, Kratassiouk G, et al. Prognostic impact of vitamin B6 metabolism in lung cancer. Cell Rep 2012; 2:257-69; PMID:22854025; http://dx.doi.org/10.1016/j.celrep.2012.06.017
223. Galluzzi L, Senovilla L, Vitale I, Michels J, Martins I, Kepp O, Castedo M, Kroemer G. Molecular mechanisms of cisplatin resistance. Oncogene 2012; 31:1869-83; PMID:21892204; http://dx.doi.org/10.1038/onc.2011.384
224. Tajeddine N, Galluzzi L, Kepp O, Hangen E, Morselli E, Senovilla L, Araujo N, Pinna G, Larochette N, Zamzami N, et al. Hierarchical involvement of Bak, VDAC1 and Bax in cisplatin-induced cell death. Oncogene 2008; 27:4221-32; PMID:18362892; http://dx.doi.org/10.1038/onc.2008.63
225. Cirone M, Garufi A, Di Renzo L, Granato M, Faggioni A, D'Orazi G. Zinc supplementation is required for the cytotoxic and immunogenic effects of chemotherapy in chemoresistant p53-functionally deficient cells. Oncoimmunology 2013; 2:e26198; PMID:24228232; http://dx.doi.org/10.4161/onci.26198
226. Pauwels B, Korst AE, Lardon F, Vermorken JB. Combined modality therapy of gemcitabine and radiation. Oncologist 2005; 10:34-51; PMID:15632251; http://dx.doi.org/10.1634/theoncologist.10-1-34
227. Heinemann V. Role of gemcitabine in the treatment of advanced and metastatic breast cancer. Oncology 2003; 64:191-206; PMID:12697958; http://dx.doi.org/10.1159/000069315
228. Rajan A, Carter CA, Kelly RJ, Gutierrez M, Kummar S, Szabo E, Yancey MA, Ji J, Mannargudi B, Woo S, et al. A phase I combination study of olaparib with cisplatin and gemcitabine in adults with solid tumors. Clin Cancer Res 2012; 18:2344-51; PMID:22371451; http://dx.doi.org/10.1158/1078-0432.CCR-11-2425
229. Pirker R, Berzinec P, Brincat S, Kasan P, Ostoros G, Pesek M, Plate S, Purkalne G, Rooneem R, Skrickova J, et al. Therapy of small cell lung cancer with emphasis on oral topotecan. Lung Cancer 2010; 70:7-13; PMID:20576312; http://dx.doi.org/10.1016/j.lungcan.2010.05.020
230. Samol J, Ranson M, Scott E, Macpherson E, Carmichael J, Thomas A, Cassidy J. Safety and tolerability of the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib (AZD2281) in combination with topotecan for the treatment of patients with advanced solid tumors: a phase I study. Invest New Drugs 2012; 30:1493-500; PMID:21590367; http://dx.doi.org/10.1007/s10637-011-9682-9
231. Kummar S, Chen A, Ji J, Zhang Y, Reid JM, Ames M, Jia L, Weil M, Speranza G, Murgo AJ, et al. Phase I study of PARP inhibitor ABT-888 in combination with topotecan in adults with refractory solid tumors and lymphomas. Cancer Res 2011; 71:5626-34; PMID:21795476; http://dx.doi.org/10.1158/0008-5472.CAN-11-1227
232. Kunos C, Deng W, Dawson D, Lea JS, Zanotti KM, Gray HJ, Bender DP, Guaglianone PP, Carter JS, Moore KN. A phase I-II evaluation of veliparib (NSC #737664), topotecan, and filgrastim or pegfilgrastim in the treatment of persistent or recurrent carcinoma of the uterine cervix: an NRG oncology/gynecologic oncology group study. Int J Gynecol Cancer 2015; 25:484-92; PMID:25594147; http://dx.doi.org/10.1097/IGC.0000000000000380
233. Su JM, Thompson P, Adesina A, Li XN, Kilburn L, Onar-Thomas A, Kocak M, Chyla B, McKeegan E, Warren KE, et al. A phase I trial of veliparib (ABT-888) and temozolomide in children with recurrent CNS tumors: a pediatric brain tumor consortium report. Neuro Oncol 2014; 16:1661-8; PMID:24908656; http://dx.doi.org/10.1093/neuonc/nou103
234. Bedikian AY, Papadopoulos NE, Kim KB, Hwu WJ, Homsi J, Glass MR, Cain S, Rudewicz P, Vernillet L, Hwu P. A phase IB trial of intravenous INO-1001 plus oral temozolomide in subjects with unresectable stage-III or IV melanoma. Cancer Invest 2009; 27:756-63; PMID:19440934; http://dx.doi.org/10.1080/07357900802709159
235. Margison GP, Santibanez Koref MF, Povey AC. Mechanisms of carcinogenicity/chemotherapy by O6-methylguanine. Mutagenesis 2002; 17:483-7; PMID:12435845; http://dx.doi.org/10.1093/mutage/17.6.483
236. Danson SJ, Middleton MR. Temozolomide: a novel oral alkylating agent. Expert Rev Anticancer Ther 2001; 1:13-9; PMID:12113120; http://dx.doi.org/10.1586/14737140.1.1.13
237. Plummer R, Lorigan P, Steven N, Scott L, Middleton MR, Wilson RH, Mulligan E, Curtin N, Wang D, Dewji R, et al. A phase II study of the potent PARP inhibitor, Rucaparib (PF-01367338, AG014699), with temozolomide in patients with metastatic melanoma demonstrating evidence of chemopotentiation. Cancer Chemother Pharmacol 2013; 71:1191-9; PMID:23423489; http://dx.doi.org/10.1007/s00280-013-2113-1
238. Balmana J, Tung NM, Isakoff SJ, Grana B, Ryan PD, Saura C, Lowe ES, Frewer P, Winer E, Baselga J, et al. Phase I trial of olaparib in combination with cisplatin for the treatment of patients with advanced breast, ovarian and other solid tumors. Ann Oncol 2014; 25:1656-63; PMID:24827126; http://dx.doi.org/10.1093/annonc/mdu187
239. Vonderheide RH, Burg JM, Mick R, Trosko JA, Li D, Shaik MN, Tolcher AW, Hamid O. Phase I study of the CD40 agonist antibody CP-870,893 combined with carboplatin and paclitaxel in patients with advanced solid tumors. Oncoimmunology 2013; 2:e23033; PMID:23483678; http://dx.doi.org/10.4161/onci.23033
240. Weiss RB, Christian MC. New cisplatin analogues in development. A review. Drugs 1993; 46:360-77; PMID:7693428; http://dx.doi.org/10.2165/00003495-199346030-00003
241. Harrap KR. Preclinical studies identifying carboplatin as a viable cisplatin alternative. Cancer Treat Rev 1985; 12:21-33; PMID:3910219; http://dx.doi.org/10.1016/0305-7372(85)90015-5
242. Lee JM, Hays JL, Annunziata CM, Noonan AM, Minasian L, Zujewski JA, Yu M, Gordon N, Ji J, Sissung TM, et al. Phase I/Ib study of olaparib and carboplatin in BRCA1 or BRCA2 mutation-associated breast or ovarian cancer with biomarker analyses. J Natl Cancer Inst 2014; 106:dju089; PMID:24842883
243. White D, Kassim A, Bhaskar B, Yi J, Wamstad K, Paton VE. Results from AMBER, a randomized phase 2 study of bevacizumab and bortezomib versus bortezomib in relapsed or refractory multiple myeloma. Cancer 2013; 119:339-47; PMID:22811009; http://dx.doi.org/10.1002/cncr.27745
244. Mansfield AS, Nevala WK, Lieser EA, Leontovich AA, Markovic SN. The immunomodulatory effects of bevacizumab on systemic immunity in patients with metastatic melanoma. Oncoimmunology 2013; 2:e24436; PMID:23762809; http://dx.doi.org/10.4161/onci.24436
245. Foy KC, Miller MJ, Moldovan N, Carson Iii WE, Kaumaya PT. Combined vaccination with HER-2 peptide followed by therapy with VEGF peptide mimics exerts effective anti-tumor and anti-angiogenic effects in vitro and in vivo. Oncoimmunology 2012; 1:1048-60; PMID:23170253; http://dx.doi.org/10.4161/onci.20708
246. Goss G, Shepherd FA, Laurie S, Gauthier I, Leighl N, Chen E, Feld R, Powers J, Seymour L. A phase I and pharmacokinetic study of daily oral cediranib, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with cisplatin and gemcitabine in patients with advanced non-small cell lung cancer: a study of the national cancer institute of canada clinical trials group. Eur J Cancer 2009; 45:782-8; PMID:19091548; http://dx.doi.org/10.1016/j.ejca.2008.10.022
247. Gomez-Rivera F, Santillan-Gomez AA, Younes MN, Kim S, Fooshee D, Zhao M, Jasser SA, Myers JN. The tyrosine kinase inhibitor, AZD2171, inhibits vascular endothelial growth factor receptor signaling and growth of anaplastic thyroid cancer in an orthotopic nude mouse model. Clin Cancer Res 2007; 13:4519-27; PMID:17671138; http://dx.doi.org/10.1158/1078-0432.CCR-06-2636
248. Wedge SR, Kendrew J, Hennequin LF, Valentine PJ, Barry ST, Brave SR, Smith NR, James NH, Dukes M, Curwen JO, et al. AZD2171: a highly potent, orally bioavailable, vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor for the treatment of cancer. Cancer Res 2005; 65:4389-400; PMID:15899831; http://dx.doi.org/10.1158/0008-5472.CAN-04-4409
249. Dean E, Middleton MR, Pwint T, Swaisland H, Carmichael J, Goodege-Kunwar P, Ranson M. Phase I study to assess the safety and tolerability of olaparib in combination with bevacizumab in patients with advanced solid tumours. Br J Cancer 2012; 106:468-74; PMID:22223088; http://dx.doi.org/10.1038/bjc.2011.555
250. Liu JF, Tolaney SM, Birrer M, Fleming GF, Buss MK, Dahlberg SE, Lee H, Whalen C, Tyburski K, Winer E, et al. A Phase 1 trial of the poly(ADP-ribose) polymerase inhibitor olaparib (AZD2281) in combination with the anti-angiogenic cediranib (AZD2171) in recurrent epithelial ovarian or triple-negative breast cancer. Eur J Cancer 2013; 49:2972-8; PMID:23810467; http://dx.doi.org/10.1016/j.ejca.2013.05.020
251. Liu JF, Barry WT, Birrer M, Lee JM, Buckanovich RJ, Fleming GF, Rimel B, Buss MK, Nattam S, Hurteau J, et al. Combination cediranib and olaparib versus olaparib alone for women with recurrent platinum-sensitive ovarian cancer: a randomised phase 2 study. Lancet Oncol 2014; 15:1207-14; PMID:25218906; http://dx.doi.org/10.1016/S1470-2045(14)70391-2
252. Hoffmann J, Vitale I, Buchmann B, Galluzzi L, Schwede W, Senovilla L, Skuballa W, Vivet S, Lichtner RB, Vicencio JM, et al. Improved cellular pharmacokinetics and pharmacodynamics underlie the wide anticancer activity of sagopilone. Cancer Res 2008; 68:5301-8; PMID:18593931; http://dx.doi.org/10.1158/0008-5472.CAN-08-0237
253. Domenech E, Malumbres M. Mitosis-targeting therapies: a troubleshooting guide. Curr Opin Pharmacol 2013; 13:519-28; PMID:23583638; http://dx.doi.org/10.1016/j.coph.2013.03.011
254. Jordan MA, Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer 2004; 4:253-65; PMID:15057285; http://dx.doi.org/10.1038/nrc1317
255. Dent RA, Lindeman GJ, Clemons M, Wildiers H, Chan A, McCarthy NJ, Singer CF, Lowe ES, Watkins CL, Carmichael J. Phase I trial of the oral PARP inhibitor olaparib in combination with paclitaxel for first- or second-line treatment of patients with metastatic triple-negative breast cancer. Breast Cancer Res 2013; 15:R88; PMID:24063698; http://dx.doi.org/10.1186/bcr3484
256. Oza AM, Cibula D, Benzaquen AO, Poole C, Mathijssen RH, Sonke GS, Colombo N, Spacek J, Vuylsteke P, Hirte H, et al. Olaparib combined with chemotherapy for recurrent platinum-sensitive ovarian cancer: a randomised phase 2 trial. Lancet Oncol 2015; 16:87-97; PMID:25481791; http://dx.doi.org/10.1016/S1470-2045(14)71135-0
257. Ziccheddu G, Proietti E, Moschella F. The Janus face of cyclophosphamide: a sterile inflammatory response that potentiates cancer immunotherapy. Oncoimmunology 2013; 2:e25789; PMID:24244905; http://dx.doi.org/10.4161/onci.25789
258. Walter S, Weinschenk T, Reinhardt C, Singh-Jasuja H. Single-dose cyclophosphamide synergizes with immune responses to the renal cell cancer vaccine IMA901. Oncoimmunology 2013; 2:e22246; PMID:23482454; http://dx.doi.org/10.4161/onci.22246
259. Chen X, Wakefield LM, Oppenheim JJ. Synergistic antitumor effects of a TGFbeta inhibitor and cyclophosphamide. Oncoimmunology 2014; 3:e28247; PMID:25050195; http://dx.doi.org/10.4161/onci.28247
260. Hussain M, Carducci MA, Slovin S, Cetnar J, Qian J, McKeegan EM, Refici-Buhr M, Chyla B, Shepherd SP, Giranda VL, et al. Targeting DNA repair with combination veliparib (ABT-888) and temozolomide in patients with metastatic castration-resistant prostate cancer. Invest New Drugs 2014; 32:904-12; PMID:24764124; http://dx.doi.org/10.1007/s10637-014-0099-0
261. Kummar S, Ji J, Morgan R, Lenz HJ, Puhalla SL, Belani CP, Gandara DR, Allen D, Kiesel B, Beumer JH, et al. A phase I study of veliparib in combination with metronomic cyclophosphamide in adults with refractory solid tumors and lymphomas. Clin Cancer Res 2012; 18:1726-34; PMID:22307137; http://dx.doi.org/10.1158/1078-0432.CCR-11-2821
262. Reiss KA, Herman JM, Zahurak M, Brade A, Dawson LA, Scardina A, Joffe C, Petito E, Hacker-Prietz A, Kinders RJ, et al. A phase I study of veliparib (ABT-888) in combination with low-dose fractionated whole abdominal radiation therapy in patients with advanced solid malignancies and peritoneal carcinomatosis. Clin Cancer Res 2015; 21:68-76; PMID:25355929; http://dx.doi.org/10.1158/1078-0432.CCR-14-1552
263. Mehta MP, Wang D, Wang F, Kleinberg L, Brade A, Robins HI, Turaka A, Leahy T, Medina D, Xiong H, et al. Veliparib in combination with whole brain radiation therapy in patients with brain metastases: results of a phase 1 study. J Neurooncol 2015; 122:409-17; PMID:25682091; http://dx.doi.org/10.1007/s11060-015-1733-1
264. Plummer R, Stephens P, Aissat-Daudigny L, Cambois A, Moachon G, Brown PD, Campone M. Phase 1 dose-escalation study of the PARP inhibitor CEP-9722 as monotherapy or in combination with temozolomide in patients with solid tumors. Cancer Chemother Pharmacol 2014; 74:257-65; PMID:24880570; http://dx.doi.org/10.1007/s00280-014-2486-9
265. Plummer R, Jones C, Middleton M, Wilson R, Evans J, Olsen A, Curtin N, Boddy A, McHugh P, Newell D, et al. Phase I study of the poly(ADP-ribose) polymerase inhibitor, AG014699, in combination with temozolomide in patients with advanced solid tumors. Clin Cancer Res 2008; 14:7917-23; PMID:19047122; http://dx.doi.org/10.1158/1078-0432.CCR-08-1223
266. Kummar S, Oza AM, Fleming GF, Sullivan DM, Gandara DR, Naughton MJ, Villalona-Calero MA, Morgan RJ, Jr., Szabo PM, Youn A, et al. Randomized trial of oral cyclophosphamide and veliparib in high-grade serous ovarian, primary peritoneal, or fallopian tube cancers, or BRCA-mutant ovarian cancer. Clin Cancer Res 2015; 21:1574-82; PMID:25589624; http://dx.doi.org/10.1158/1078-0432.CCR-14-2565
267. Walko CM, Lindley C. Capecitabine: a review. Clin Ther 2005; 27:23-44; PMID:15763604; http://dx.doi.org/10.1016/j.clinthera.2005.01.005
268. Grossi F, Aita M, Defferrari C, Rosetti F, Brianti A, Fasola G, Vinante O, Pronzato P, Pappagallo G. Impact of third-generation drugs on the activity of first-line chemotherapy in advanced non-small cell lung cancer: a meta-analytical approach. Oncologist 2009; 14:497-510; PMID:19423674; http://dx.doi.org/10.1634/theoncologist.2008-0260
269. Himes RH. Interactions of the catharanthus (Vinca) alkaloids with tubulin and microtubules. Pharmacol Ther 1991; 51:257-67; PMID:1784631; http://dx.doi.org/10.1016/0163-7258(91)90081-V
270. Roche H, Blum J, Eiermann W, Im YH, Martin M, Mina L, Rugo H, Visco F, Zhang C, Lokker N, et al. P1.01A phase 3 study of the oral PARP inhibitor talazoparib (BMN 673) in BRCA mutation subjects with advanced breast cancer (EMBRACA). Ann Oncol 2015; 26 2:ii16
271. Goss PE, Ingle JN, Pater JL, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Shepherd LE, Pritchard KI, et al. Late extended adjuvant treatment with letrozole improves outcome in women with early-stage breast cancer who complete 5 years of tamoxifen. J Clin Oncol 2008; 26:1948-55; PMID:18332475; http://dx.doi.org/10.1200/JCO.2007.11.6798
272. Forbes JF, Cuzick J, Buzdar A, Howell A, Tobias JS, Baum M. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol 2008; 9:45-53; PMID:18083636; http://dx.doi.org/10.1016/S1470-2045(07)70385-6
273. Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes JF, Hoctin-Boes G, Houghton J, Locker GY, Tobias JS. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet 2005; 365:60-2; PMID:15639680; http://dx.doi.org/10.1016/S0140-6736(05)74803-0
274. Davies C, Godwin J, Gray R, Clarke M, Cutter D, Darby S, McGale P, Pan HC, Taylor C, Wang YC, et al. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 2011; 378:771-84; PMID:21802721; http://dx.doi.org/10.1016/S0140-6736(11)60993-8
275. Kim DJ, Kim J, Spaunhurst K, Montoya J, Khodosh R, Chandra K, Fu T, Gilliam A, Molgo M, Beachy PA, et al. Open-label, exploratory phase II trial of oral itraconazole for the treatment of basal cell carcinoma. J Clin Oncol 2014; 32:745-51; PMID:24493717; http://dx.doi.org/10.1200/JCO.2013.49.9525
276. Rudin CM, Brahmer JR, Juergens RA, Hann CL, Ettinger DS, Sebree R, Smith R, Aftab BT, Huang P, Liu JO. Phase 2 study of pemetrexed and itraconazole as second-line therapy for metastatic nonsquamous non-small-cell lung cancer. J Thorac Oncol 2013; 8:619-23; PMID:23546045
277. Kim J, Tang JY, Gong R, Kim J, Lee JJ, Clemons KV, Chong CR, Chang KS, Fereshteh M, Gardner D, et al. Itraconazole, a commonly used antifungal that inhibits Hedgehog pathway activity and cancer growth. Cancer Cell 2010; 17:388-99; PMID:20385363; http://dx.doi.org/10.1016/j.ccr.2010.02.027
278. Niemi M, Backman JT, Fromm MF, Neuvonen PJ, Kivisto KT. Pharmacokinetic interactions with rifampicin: clinical relevance. Clin Pharmacokinet 2003; 42:819-50; PMID:12882588; http://dx.doi.org/10.2165/00003088-200342090-00003
279. Liao H, Huang Y, Guo B, Liang B, Liu X, Ou H, Jiang C, Li X, Yang D. Dramatic antitumor effects of the dual mTORC1 and mTORC2 inhibitor AZD2014 in hepatocellular carcinoma. Am J Cancer Res 2015; 5:125-39; PMID:25628925
280. Addie M, Ballard P, Buttar D, Crafter C, Currie G, Davies BR, Debreczeni J, Dry H, Dudley P, Greenwood R, et al. Discovery of 4-amino-N-; [(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo; [2,3-d]pyrimidin -4-yl)piperidine-4-carboxamide (AZD5363), an orally bioavailable, potent inhibitor of Akt kinases. J Med Chem 2013; 56:2059-73; PMID:23394218; http://dx.doi.org/10.1021/jm301762v
281. Pike KG, Malagu K, Hummersone MG, Menear KA, Duggan HM, Gomez S, Martin NM, Ruston L, Pass SL, Pass M. Optimization of potent and selective dual mTORC1 and mTORC2 inhibitors: the discovery of AZD8055 and AZD2014. Bioorg Med Chem Lett 2013; 23:1212-6; PMID:23375793; http://dx.doi.org/10.1016/j.bmcl.2013.01.019
282. Davies BR, Greenwood H, Dudley P, Crafter C, Yu DH, Zhang J, Li J, Gao B, Ji Q, Maynard J, et al. Preclinical pharmacology of AZD5363, an inhibitor of AKT: pharmacodynamics, antitumor activity, and correlation of monotherapy activity with genetic background. Mol Cancer Ther 2012; 11:873-87; PMID:22294718; http://dx.doi.org/10.1158/1535-7163.MCT-11-0824-T
283. Burger MT, Pecchi S, Wagman A, Ni ZJ, Knapp M, Hendrickson T, Atallah G, Pfister K, Zhang Y, Bartulis S, et al. Identification of NVP-BKM120 as a potent, selective, orally bioavailable class I PI3 kinase inhibitor for treating cancer. ACS Med Chem Lett 2011; 2:774-9; PMID:24900266; http://dx.doi.org/10.1021/ml200156t
284. Reid AH, Attard G, Barrie E, de Bono JS. CYP17 inhibition as a hormonal strategy for prostate cancer. Nat Clin Pract Urol 2008; 5:610-20; PMID:18985049; http://dx.doi.org/10.1038/ncpuro1237
285. Raab MS, Podar K, Breitkreutz I, Richardson PG, Anderson KC. Multiple myeloma. Lancet 2009; 374:324-39; PMID:19541364; http://dx.doi.org/10.1016/S0140-6736(09)60221-X
286. Ranney HM, Gellhorn A. The effect of massive prednisone and prednisolone therapy on acute leukemia and malignant lymphomas. Am J Med 1957; 22:405-13; PMID:13402792; http://dx.doi.org/10.1016/0002-9343(57)90096-7
287. Carter NJ, Keam SJ. Degarelix: a review of its use in patients with prostate cancer. Drugs 2014; 74:699-712; PMID:24756432; http://dx.doi.org/10.1007/s40265-014-0211-y
288. Steinberg M. Degarelix: a gonadotropin-releasing hormone antagonist for the management of prostate cancer. Clin Ther 2009; 31 2:2312-31; PMID:20110043; http://dx.doi.org/10.1016/j.clinthera.2009.11.009
289. Power DG, Kemeny NE. The role of floxuridine in metastatic liver disease. Mol Cancer Ther 2009; 8:1015-25; PMID:19383854; http://dx.doi.org/10.1158/1535-7163.MCT-08-0709
290. Twelves C, Wong A, Nowacki MP, Abt M, Burris H, 3rd, Carrato A, Cassidy J, Cervantes A, Fagerberg J, Georgoulias V, et al. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med 2005; 352:2696-704; PMID:15987918; http://dx.doi.org/10.1056/NEJMoa043116
291. Meyerhardt JA, Mayer RJ. Systemic therapy for colorectal cancer. N Engl J Med 2005; 352:476-87; PMID:15689586; http://dx.doi.org/10.1056/NEJMra040958
292. Cersosimo RJ. Management of advanced colorectal cancer, Part 2. Am J Health Syst Pharm 2013; 70:491-506; PMID:23456402; http://dx.doi.org/10.2146/ajhp110532b
293. Cersosimo RJ. Management of advanced colorectal cancer, Part 1. Am J Health Syst Pharm 2013; 70:395-406; PMID:23413162; http://dx.doi.org/10.2146/ajhp110532
294. Culy CR, Clemett D, Wiseman LR. Oxaliplatin. a review of its pharmacological properties and clinical efficacy in metastatic colorectal cancer and its potential in other malignancies. Drugs 2000; 60:895-924; PMID:11085200; http://dx.doi.org/10.2165/00003495-200060040-00005
295. Raymond E, Faivre S, Chaney S, Woynarowski J, Cvitkovic E. Cellular and molecular pharmacology of oxaliplatin. Mol Cancer Ther 2002; 1:227-35; PMID:12467217
296. Bruserud O, Reikvam H, Kittang AO, Ahmed AB, Tvedt TH, Sjo M, Hatfield KJ. High-dose etoposide in allogeneic stem cell transplantation. Cancer Chemother Pharmacol 2012; 70:765-82; PMID:23053272; http://dx.doi.org/10.1007/s00280-012-1990-z
297. Montecucco A, Biamonti G. Cellular response to etoposide treatment. Cancer Lett 2007; 252:9-18; PMID:17166655; http://dx.doi.org/10.1016/j.canlet.2006.11.005
298. Josephs DH, Fisher DS, Spicer J, Flanagan RJ. Clinical pharmacokinetics of tyrosine kinase inhibitors: implications for therapeutic drug monitoring. Ther Drug Monit 2013; 35:562-87; PMID:24052062
299. Johnston S, Pippen J, Jr., Pivot X, Lichinitser M, Sadeghi S, Dieras V, Gomez HL, Romieu G, Manikhas A, Kennedy MJ, et al. Lapatinib combined with letrozole versus letrozole and placebo as first-line therapy for postmenopausal hormone receptor-positive metastatic breast cancer. J Clin Oncol 2009; 27:5538-46; PMID:19786658; http://dx.doi.org/10.1200/JCO.2009.23.3734
300. Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, Jagiello-Gruszfeld A, Crown J, Chan A, Kaufman B, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med 2006; 355:2733-43; PMID:17192538; http://dx.doi.org/10.1056/NEJMoa064320
301. Konecny GE, Pegram MD, Venkatesan N, Finn R, Yang G, Rahmeh M, Untch M, Rusnak DW, Spehar G, Mullin RJ, et al. Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. Cancer Res 2006; 66:1630-9; PMID:16452222; http://dx.doi.org/10.1158/0008-5472.CAN-05-1182
302. Montoni A, Robu M, Pouliot E, Shah GM. Resistance to PARP-Inhibitors in Cancer Therapy. Front Pharmacol 2013; 4:18; PMID:23450678; http://dx.doi.org/10.3389/fphar.2013.00018
303. Barber LJ, Sandhu S, Chen L, Campbell J, Kozarewa I, Fenwick K, Assiotis I, Rodrigues DN, Reis Filho JS, Moreno V, et al. Secondary mutations in BRCA2 associated with clinical resistance to a PARP inhibitor. J Pathol 2013; 229:422-9; PMID:23165508; http://dx.doi.org/10.1002/path.4140
304. Edwards SL, Brough R, Lord CJ, Natrajan R, Vatcheva R, Levine DA, Boyd J, Reis-Filho JS, Ashworth A. Resistance to therapy caused by intragenic deletion in BRCA2. Nature 2008; 451:1111-5; PMID:18264088; http://dx.doi.org/10.1038/nature06548
305. Jaspers JE, Kersbergen A, Boon U, Sol W, van Deemter L, Zander SA, Drost R, Wientjens E, Ji J, Aly A, et al. Loss of 53BP1 causes PARP inhibitor resistance in Brca1-mutated mouse mammary tumors. Cancer Discov 2013; 3:68-81; PMID:23103855; http://dx.doi.org/10.1158/2159-8290.CD-12-0049
306. Bunting SF, Callen E, Wong N, Chen HT, Polato F, Gunn A, Bothmer A, Feldhahn N, Fernandez-Capetillo O, Cao L, et al. 53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaks. Cell 2010; 141:243-54; PMID:20362325; http://dx.doi.org/10.1016/j.cell.2010.03.012
307. Xu G, Chapman JR, Brandsma I, Yuan J, Mistrik M, Bouwman P, Bartkova J, Gogola E, Warmerdam D, Barazas M, et al. REV7 counteracts DNA double-strand break resection and affects PARP inhibition. Nature 2015; PMID:25799992
308. Rottenberg S, Jaspers JE, Kersbergen A, van der Burg E, Nygren AO, Zander SA, Derksen PW, de Bruin M, Zevenhoven J, Lau A, et al. High sensitivity of BRCA1-deficient mammary tumors to the PARP inhibitor AZD2281 alone and in combination with platinum drugs. Proc Natl Acad Sci U S A 2008; 105:17079-84; PMID:18971340; http://dx.doi.org/10.1073/pnas.0806092105
309. Leung AK, Vyas S, Rood JE, Bhutkar A, Sharp PA, Chang P. Poly(ADP-ribose) regulates stress responses and microRNA activity in the cytoplasm. Mol Cell 2011; 42:489-99; PMID:21596313; http://dx.doi.org/10.1016/j.molcel.2011.04.015
310. Green DR, Galluzzi L, Kroemer G. Cell biology. Metabolic control of cell death. Science 2014; 345:1250256; PMID:25237106; http://dx.doi.org/10.1126/science.1250256
311. Kanai M, Tong WM, Sugihara E, Wang ZQ, Fukasawa K, Miwa M. Involvement of poly(ADP-Ribose) polymerase 1 and poly(ADP-Ribosyl)ation in regulation of centrosome function. Mol Cell Biol 2003; 23:2451-62; PMID:12640128; http://dx.doi.org/10.1128/MCB.23.7.2451-2462.2003
312. Kanai M, Tong WM, Wang ZQ, Miwa M. Haploinsufficiency of poly(ADP-ribose) polymerase-1-mediated poly(ADP-ribosyl)ation for centrosome duplication. Biochem Biophys Res Commun 2007; 359:426-30; PMID:17553458; http://dx.doi.org/10.1016/j.bbrc.2007.05.108
313. Simbulan-Rosenthal CM, Ly DH, Rosenthal DS, Konopka G, Luo R, Wang ZQ, Schultz PG, Smulson ME. Misregulation of gene expression in primary fibroblasts lacking poly(ADP-ribose) polymerase. Proc Natl Acad Sci U S A 2000; 97:11274-9; PMID:11016956; http://dx.doi.org/10.1073/pnas.200285797
314. Halappanavar SS, Shah GM. Defective control of mitotic and post-mitotic checkpoints in poly(ADP-ribose) polymerase-1(−/−) fibroblasts after mitotic spindle disruption. Cell Cycle 2004; 3:335-42; PMID:14726664; http://dx.doi.org/10.4161/cc.3.3.670
315. Inbar D, Cohen-Armon M, Neumann D. Erythropoietin-driven signalling and cell migration mediated by polyADP-ribosylation. Br J Cancer 2012; 107:1317-26; PMID:22955851; http://dx.doi.org/10.1038/bjc.2012.395
316. Caldini R, Fanti E, Magnelli L, Barletta E, Tanganelli E, Zampieri M, Chevanne M. Low doses of 3-aminobenzamide, a poly(ADP-ribose) polymerase inhibitor, stimulate angiogenesis by regulating expression of urokinase type plasminogen activator and matrix metalloprotease 2. Vasc Cell 2011; 3:12; PMID:21595892; http://dx.doi.org/10.1186/2045-824X-3-12
317. Lacal PM, Tentori L, Muzi A, Ruffini F, Dorio AS, Xu W, Arcelli D, Zhang J, Graziani G. Pharmacological inhibition of poly(ADP-ribose) polymerase activity down-regulates the expression of syndecan-4 and Id-1 in endothelial cells. Int J Oncol 2009; 34:861-72; PMID:19212692
318. Tentori L, Lacal PM, Muzi A, Dorio AS, Leonetti C, Scarsella M, Ruffini F, Xu W, Min W, Stoppacciaro A, et al. Poly(ADP-ribose) polymerase (PARP) inhibition or PARP-1 gene deletion reduces angiogenesis. Eur J Cancer 2007; 43:2124-33; PMID:17714938; http://dx.doi.org/10.1016/j.ejca.2007.07.010
319. Pyriochou A, Olah G, Deitch EA, Szabo C, Papapetropoulos A. Inhibition of angiogenesis by the poly(ADP-ribose) polymerase inhibitor PJ-34. Int J Mol Med 2008; 22:113-8; PMID:18575783
320. Rajesh M, Mukhopadhyay P, Godlewski G, Batkai S, Hasko G, Liaudet L, Pacher P. Poly(ADP-ribose)polymerase inhibition decreases angiogenesis. Biochem Biophys Res Commun 2006; 350:1056-62; PMID:17046715; http://dx.doi.org/10.1016/j.bbrc.2006.09.160
321. Li Q, Li M, Wang YL, Fauzee NJ, Yang Y, Pan J, Yang L, Lazar A. RNA interference of PARG could inhibit the metastatic potency of colon carcinoma cells via PI3-kinase/Akt pathway. Cell Physiol Biochem 2012; 29:361-72; PMID:22508044; http://dx.doi.org/10.1159/000338491
322. Riffell JL, Lord CJ, Ashworth A. Tankyrase-targeted therapeutics: expanding opportunities in the PARP family. Nat Rev Drug Discov 2012; 11:923-36; PMID:23197039; http://dx.doi.org/10.1038/nrd3868
323. Stilmann M, Hinz M, Arslan SC, Zimmer A, Schreiber V, Scheidereit C. A nuclear poly(ADP-ribose)-dependent signalosome confers DNA damage-induced IkappaB kinase activation. Mol Cell 2009; 36:365-78; PMID:19917246; http://dx.doi.org/10.1016/j.molcel.2009.09.032
324. Cohen-Armon M, Visochek L, Rozensal D, Kalal A, Geistrikh I, Klein R, Bendetz-Nezer S, Yao Z, Seger R. DNA-independent PARP-1 activation by phosphorylated ERK2 increases Elk1 activity: a link to histone acetylation. Mol Cell 2007; 25:297-308; PMID:17244536; http://dx.doi.org/10.1016/j.molcel.2006.12.012
325. Kauppinen TM, Chan WY, Suh SW, Wiggins AK, Huang EJ, Swanson RA. Direct phosphorylation and regulation of poly(ADP-ribose) polymerase-1 by extracellular signal-regulated kinases 1/2. Proc Natl Acad Sci U S A 2006; 103:7136-41; PMID:16627622; http://dx.doi.org/10.1073/pnas.0508606103
326. Shimo T, Kurebayashi J, Kanomata N, Yamashita T, Kozuka Y, Moriya T, Sonoo H. Antitumor and anticancer stem cell activity of a poly ADP-ribose polymerase inhibitor olaparib in breast cancer cells. Breast Cancer 2014; 21:75-85; PMID:22454224; http://dx.doi.org/10.1007/s12282-012-0356-z
327. Jwa M, Chang P. PARP16 is a tail-anchored endoplasmic reticulum protein required for the PERK- and IRE1alpha-mediated unfolded protein response. Nat Cell Biol 2012; 14:1223-30; PMID:23103912; http://dx.doi.org/10.1038/ncb2593
328. El-Hamoly T, Hegedus C, Lakatos P, Kovacs K, Bai P, El-Ghazaly MA, El-Denshary ES, Szabo E, Virag L. Activation of poly(ADP-ribose) polymerase-1 delays wound healing by regulating keratinocyte migration and production of inflammatory mediators. Mol Med 2014; 20:363-71; PMID:25014793; http://dx.doi.org/10.2119/molmed.2014.00130
329. Bendell J, O'Reilly EM, Middleton MR, Chau I, Hochster H, Fielding A, Burke W, Burris H, 3rd. Phase I study of olaparib plus gemcitabine in patients with advanced solid tumours and comparison with gemcitabine alone in patients with locally advanced/metastatic pancreatic cancer. Ann Oncol 2015; 26:804-11; PMID:25573533; http://dx.doi.org/10.1093/annonc/mdu581
330. Kummar S, Kinders R, Gutierrez ME, Rubinstein L, Parchment RE, Phillips LR, Ji J, Monks A, Low JA, Chen A, et al. Phase 0 clinical trial of the poly (ADP-ribose) polymerase inhibitor ABT-888 in patients with advanced malignancies. J Clin Oncol 2009; 27:2705-11; PMID:19364967; http://dx.doi.org/10.1200/JCO.2008.19.7681