DNA damage response and prostate cancer: Defects, regulation and therapeutic implications

Oncogene

Volumn 34, Issue 22, 2015, Pages 2815-2822

  Karanika, S ^a   Karantanos, T ^a   Li, L ^a   Corn, P G ^a   Thompson, T C ^a  

^a UNIVERSITY OF TEXAS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROGEN RECEPTOR; ANDROGEN RECEPTOR ANTAGONIST; CHECKPOINT KINASE 1; PROTEIN KINASE B; AR PROTEIN, HUMAN; DNA;

CANCER CELL; CANCER GROWTH; CELL CYCLE CHECKPOINT; CYTOTOXICITY; DNA DAMAGE; DNA REPAIR; GENOMIC INSTABILITY; HOMOLOGOUS RECOMBINATION; HUMAN; LETHALITY; ONCOGENE C MYC; PRIORITY JOURNAL; PROSTATE CANCER; REVIEW; SIGNAL TRANSDUCTION; TUMOR SUPPRESSOR GENE; ANIMAL; BIOSYNTHESIS; DNA REPLICATION; GENE EXPRESSION REGULATION; GENETICS; MALE; PHYSIOLOGY; PROSTATIC NEOPLASMS;

ANIMALS; CELL CYCLE CHECKPOINTS; DNA DAMAGE; DNA REPAIR; DNA REPLICATION; DNA, NEOPLASM; GENE EXPRESSION REGULATION, NEOPLASTIC; GENOMIC INSTABILITY; HUMANS; MALE; PROSTATIC NEOPLASMS; RECEPTORS, ANDROGEN;

EID: 84930084362     PISSN: 09509232     EISSN: 14765594     Source Type: Journal    
DOI: 10.1038/onc.2014.238     Document Type: Review

References (106)

1. Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. New Engl J Med 2013; 368: 138-148.
2. Fizazi K, Scher HI, Molina A, Logothetis CJ, Chi KN, Jones RJ et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebocontrolled phase 3 study. Lancet Oncol 2012; 13: 983-992.
3. Beer TM, Armstrong AJ, Sternberg CN, Higano CS, Iversen P, Loriot Y et al. Enzalutamide in men with chemotherapy-naïve metastatic prostate cancer (mCRPC): results of phase 3 PREVAIL study. Presented at 2014 Genitourinary Cancers Symposium; 30 January-1 February 2014; San Francisco, CA, USA.
4. Scher HI, Fizazi K, Saad F, Taplin ME, Sterberg CN, Miller K et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. New Engl J Med 2012; 367: 1187-1197.
5. Bolla M, Gonzalez D, Warde P, Dubois JB, Mirimanoff RO, Storme G et al. Improved survival in patients with locally advanced prostate cancer treated with radiotherapy and goserelin. New Engl J Med 1997; 337: 295-300.
6. Polkinghorn WR, Parker JS, Lee MX, Kass EM, Spratt DE, Iaquinta PJ et al. Androgen receptor signaling regulates DNA repair in prostate cancers. Cancer Discov 2013; 3: 1245-1253.
7. Goodwin JF, Schiewer MJ, Dean JL, Schrecengost RS, de Leeuw R, Han S et al. A hormone-DNA repair circuit governs the response to genotoxic insult. Cancer Discov 2013; 3: 1254-1271.
8. Lord CJ, Ashworth A. The DNA damage response and cancer therapy. Nature 2012; 481: 287-294.
9. Ciccia A, Elledge SJ. The DNA damage response: making it safe to play with knives. Mol Cell 2010; 40: 179-204.
10. D'Adda di Fagagna F. Living on a break: cellular senescence as a DNA-damage response. Nat Rev Cancer 2008; 8: 512-522.
11. Taylor RC, Cullen SP, Martin SJ. Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol 2008; 9: 231-241.
12. Smith J1, Tho LM, Xu N, Gillespie DA. The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer. Adv Cancer Res. 2010; 108: 73-112.
13. Martín Y, Domínguez-Kelly R, Freire R. Novel insights into maintaining genomic integrity: Wee1 regulating Mus81/Eme1. Cell Div 2011; 6: 21.
14. Do K, Doroshow JH, Kummar S. Wee1 kinase as a target for cancer therapy. Cell Cycle 2013; 12: 3159-3164.
15. Ma CX, Janetka JW, Piwnica-Worms H. Death by releasing the breaks: CHK1 inhibitors as cancer therapeutics. Trends Mol Med 2011; 17: 88-96.
16. Moynahan ME, Jasin M. Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis. Nat Rev Mol Cell Biol 2010; 11: 196-207.
17. Lieber MR. NHEJ and its backup pathways in chromosomal translocations. Nat Struct Mol Biol 2010; 17: 393-395.
18. Dvir A, Peterson SR, Knuth MW, Lu H, Dynan WS. Ku autoantigen is the regulatory component of a template-associated protein kinase that phosphorylates RNA polymerase II. Proc Natl Acad Sci USA 1992; 89: 11920-11924.
19. Heaphy CM, Yoon GS, Peskoe SB, Joshu CE, Lee TK, Giovannucci E et al. Prostate cancer cell telomere length variability and stromal cell telomere length as prognostic markers for metastasis and death. Cancer Discov 2013; 3: 1130-1141.
20. Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature 2011; 474: 609-615.
21. Leongamornlert D, Mahmud N, Tymrakiewicz M, Saunders E, Dadaev T, Castro E et al. Germline BRCA1 mutations increase prostate cancer risk. Br J Cancer 2012; 106: 1697-1701.
22. van Asperen CJ, Brohet RM, Meijers-Heijboer EJ, Hoogerbrugge N, Verhoef S, Vasen HF et al. Cancer risks in BRCA2 families: estimates for sites other than breast and ovary. J Med Genet 2005; 42: 711-719.
23. Ding L, Getz G, Wheeler DA, Mardis ER, McLellan MD, Cibulskis K et al. Somatic mutations affect key pathways in lung adenocarcinoma. Nature 2008; 455: 1069-7.
24. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G et al. Patterns of somatic mutation in human cancer genomes. Nature 2007; 446: 153-158.
25. Beltran H, Yelensky R, Frampton GM, Park K, Downing SR, MacDonald TY et al. Targeted next-generation sequencing of advanced prostate cancer identifies potential therapeutic targets and disease heterogeneity. Eur Urol 2013; 63: 920-926.
26. Bartkova J, Rezaei N, Liontos M, Karakaidos P, Kletsas D, Issaeva N et al. Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 2006; 444: 633-637.
27. Halazonetis TD, Gorgoulis VG, Bartek J. An oncogene-induced DNA damage model for cancer development. Science 2008; 319: 1352-1355.
28. Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 2005; 434: 917-921.
29. Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E et al. Specific killing of BRCA2-deficient tumors with inhibitors of poly(ADP-ribose) polymerase. Nature 2005; 434: 913-917.
30. Campaner S, Amati B. Two sides of the Myc-induced DNA damage response: from tumor suppression to tumor maintenance. Cell Div 2012; 7: 6.
31. Ferrao PT, Bukczynska EP, Johnstone RW, McArthur GA. Efficacy of CHK inhibitors as single agents in MYC-driven lymphoma cells. Oncogene 2012; 31: 1661-1672.
32. Abulaiti A, Fikaris AJ, Tsygankova OM, Meinkoth JL. Ras induces chromosome instability and abrogation of the DNA damage response. Cancer Res 2006; 66: 10505-10512.
33. Curtin NJ. DNA repair dysregulation from cancer driver to therapeutic target. Nat Rev Cancer 2012; 12: 801-817.
34. Lukas C, Melander F, Stucki M, Falck J, Bekker-Jensen S, Goldberg M et al. Mdc1 couples DNA double-strand break recognition by Nbs1 with its H2AX-dependent chromatin retention. EMBO J 2004; 23: 2674-2683.
35. Elkahwaji JE. The role of inflammatory mediators in the development of prostatic hyperplasia and prostate cancer. Res Rep Urol 2012; 5: 1-10.
36. Balistreri CR, Candore G, Lio D, Carruba G. Prostate cancer: from the pathophysiologic implications of some genetic risk factors to translation in personalized cancer treatments. Cancer Gene Ther 2014; 21: 2-11.
37. Malins DC, Johnson PM, Wheeler TM, Barker EA, Polissar NL, Vinson M. A. Agerelated radical-induced DNA damage is linked to prostate cancer. Cancer Res 2001; 61: 6025-6028.
38. Malins DC, Johnson PM, Barker EA, Polissar NL, Wheeler TM, Anderson KM. Cancer-related changes in prostate DNA as men age and early identification of metastasis in primary prostate tumors. Proc Natl Acad Sci USA 2003; 100: 5401-5406.
39. De Marzo AM, Platz EA, Sutcliffe S, Xu J, Gronberg H, Drake CG et al. Inflammation in prostate carcinogenesis. Nat Rev Cancer 2007; 7: 256-269.
40. Sciarra A, Di Silverio F, Salciccia S, Autran Gomez AM, Gentilucci A, Gentile V. Inflammation and chronic prostatic diseases: evidence for a link? Eur Urol 2007; 52: 964-972.
41. Debelec-Butuner B, Alapinar C, Varisli L, Erbaykent-Tepedelen B, Hamid SM, Gonen-Korkmaz C et al. Inflammation-mediated abrogation of androgen signaling: an in vitro model of prostate cell inflammation. Mol Carcinog 2014; 53: 85-97.
42. Ide H, Lu Y, Yu J, China T, Kumamoto T, Koseki T et al. Testosterone promotes DNA damage response under oxidative stress in prostate cancer cell lines. Prostate 2012; 72: 1407-1411.
43. Imamoto T, Suzuki H, Yano M, Kawamura K, Kamiya N, Araki K et al. The role of testosterone in the pathogenesis of prostate cancer. Int J Urol 2008; 15: 472-480.
44. Schatzl G, Madersbacher S, Thurridl T, Waldmüller J, Kramer G, Haitel A et al. High-grade prostate cancer is associated with low serum testosterone levels. Prostate 2001; 47: 52-58.
45. Albisinni S, De Nunzio C, Tubaro A, Barry WT, Banez LL, Freedland SJ. Greater percent-free testosterone is associated with high-grade prostate cancer in men undergoing prostate biopsy. Urology 2012; 80: 162-167.
46. Zhou J, Richardson M, Reddy V, Menon M, Barrack ER, Reddy GP et al. Structural and functional association of androgen receptor with telomeres in prostate cancer cells. Aging (Albany NY) 2013; 5: 3-17.
47. Bowen C, Ju JH, Lee JH, Paul TT, Gelmann EP. Functional activation of ATM by the prostate cancer suppressor NKX3.1. Cell Rep 2013; 4: 516-529.
48. Dombernowsky SL, Weischer M, Allin KH, Bojesen SE, Tybjaerg-Hansen A, Nordestgaard BG. Risk of cancer by ATM missense mutations in the general population. J ClinOncol 2008; 26: 3057-3062.
49. Angèle S, Falconer A, Edwards SM, Dörk T, Bremer M, Moullan N et al. ATM polymorphisms as risk factors for prostate cancer development. Br J Cancer 2004; 91: 783-787.
50. Khandrika L, Kumar B, Koul S, Maroni P, Koul HK. Oxidative stress in prostate cancer. Cancer Lett 2009; 282: 125-136.
51. Taylor BS, Schultz N, Hieronymus H, Gopalan A, Xiao Y, Carver BS et al. Integrative genomic profiling of human prostate cancer. Cancer Cell 2010; 18: 11-22.
52. Muller PAJ, Vousden KH. p53 mutations in cancer. Nat Cell Biol 2013; 15: 2-8.
53. Schlomm T, Iwers L, Kirstein P, Jessen B, Köllermann J, Minner S et al. Clinical significance of p53 alterations in surgically treated prostate cancers. Mod Pathol 2008; 21: 1371-1378.
54. Eastham JA, Stapleton AM, Gousse AE, Timme TL. Association of p53 mutations with metastatic prostate cancer. Clin Cancer Res 1995; 1: 1111-1118.
55. Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig RW. Participation of p53 protein in the cellular response to DNA damage. Cancer Res 1991; 51: 6304-6311.
56. Maltzman W, Czyzyk L. UV irradiation stimulates levels of p53 cellular tumor antigen in nontransformed mouse cells. Mol Cell Biol 1984; 4: 1689-1694.
57. Linke SP, Clarkin KC, Di Leonardo A, Tsou A, Wahl GM. A reversible, p53-dependent G0/G1 cell cycle arrest induced by ribonucleotide depletion in the absence of detectable DNA damage. Genes Dev 1996; 10: 934-947.
58. Reinhardt HC, Schumacher B. The p53 network: cellular and systemic DNA damage responses in aging and cancer. Trends Genet 2012; 28: 128-136.
59. Gabrielli B, Brooks K, Pavey S. Defective cell cycle checkpoints as targets for anticancer therapies. Front Pharmacol 2012; 3: 9.
60. Dong X, Wang L, Taniguchi K, Wang X, Cunningham JM, McDonnell SK et al. Mutations in CHEK2 associated with prostate cancer risk. Am J Hum Genet 2003; 72: 270-280.
61. Ma CX1, Cai S, Li S, Ryan CE, Guo Z, Schaiff WT, Lin L et al. Targeting Chk1 in p53-deficient triple-negative breast cancer is therapeutically beneficial in human-in-mouse tumor models. J Clin Invest 2012; 122: 1541-1552.
62. Chen Z, Xiao Z, Gu WZ, Xue J, Bui MH, Kovar P, Li G, Wang G et al. Selective Chk1 inhibitors differentially sensitize p53-deficient cancer cells to cancer therapeutics. Int J Cancer 2006; 119: 2784-2794.
63. Wang X, Ma Z, Xiao Z, Liu H, Dou Z, Feng X, Shi H. Chk1 knockdown confers radiosensitization in prostate cancer stem cells. Oncol Rep 2012; 28: 2247-2254.
64. Landau HJ, McNeely SC, Nair JS, Comenzo RL, Asai T, Friedman H et al. The checkpoint kinase inhibitor AZD7762 potentiates chemotherapy-induced apoptosis of p53-mutated multiple myeloma cells. Mol Cancer Ther 2012; 11: 1781-1788.
65. Iglehart JD, Silver DP. Synthetic lethality-a new direction in cancer-drug development. New Engl J Med 2009; 361: 189-191.
66. Fong PC, Boss DS, Yap TA, Tutt A, Wu P, Mergui-Roelvink M et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. New Engl J Med 2009; 361: 123-134.
67. Thompson D, Easton DF. Cancer incidence in BRCA1 mutation carriers. J Natl Cancer Inst 2002; 94: 1358-1365.
68. Sandhu SK, Omlin A, Hylands L, Miranda S, Barber LJ, Riisnaes R et al. Poly (ADPribose) polymerase (PARP) inhibitors for the treatment of advanced germline BRCA2 mutant prostate cancer. Ann Oncol 2013; 24: 1416-1418.
69. Thompson TC, Southgate J, Kitchener G, Land H. Multistage carcinogenesis induced by ras and myc oncogenes in a reconstituted organ. Cell 1989; 56: 917-930.
70. Chen Z, Trotman LC, Shaffer D, Lin HK, Dotan ZA, Niki M et al. Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature 2005; 436: 725-730.
71. Mulholland DJ, Kobayashi N, Ruscetti M, Zhi A, Tran LM, Huang J et al. Pten loss and RAS/MAPK activation cooperate to promote EMT and metastasis initiated from prostate cancer stem/progenitor cells. Cancer Res 2012; 72: 1878-1889.
72. Kim J, Roh M, Doubinskaia I, Algarroba GN, Eltoum IE, Abdulkadir SA. A mouse model of heterogeneous, c-MYC-initiated prostate cancer with loss of Pten and p53. Oncogene 2012; 31: 322-332.
73. Ding Z, Wu CJ, Jaskelioff M, Ivanova E, Kost-Alimova M, Protopopov A et al. Telomerase reactivation following telomere dysfunction yields murine prostate tumors with bone metastases. Cell 2012; 148: 896-907.
74. Karantanos T, Corn PG, Thompson TC. Prostate cancer progression after androgen deprivation therapy: mechanisms of castrate resistance and novel therapeutic approaches. Oncogene 2013; 32: 5501-5511.
75. Puc J, Keniry M, Li HS, Pandita TK, Choudhury AD, Memeo L et al. Lack of PTEN sequesters CHK1 and initiates genetic instability. Cancer Cell 2005; 7: 193-204.
76. Barré B, Perkins ND. A cell cycle regulatory network controlling NF-?B subunit activity and function. EMBO J 2007; 26: 4841-4855.
77. Pedram A, Razandi M, Evinger AJ, Lee E, Levin ER. Estrogen inhibits ATR signaling to cell cycle checkpoints and DNA repair. Mol Biol Cell 2009; 20: 3374-3389.
78. Tonic I, Yu WN, Park Y, Chen CC, Hay N. Akt activation emulates Chk1 inhibition and Bcl2 overexpression and abrogates G2 cell cycle checkpoint by inhibiting BRCA1 foci. J Biol Chem 2010; 285: 23790-23798.
79. Plo I, Laulier C, Gauthier L, Lebrun F, Calvo F, Lopez BS. AKT1 inhibits homologous recombination by inducing cytoplasmic retention of BRCA1 and RAD51. Cancer Res 2008; 68: 9404-9412.
80. Plo I, Lopez B. AKT1 represses gene conversion induced by different genotoxic stresses and induces supernumerary centrosomes and aneuploidy in hamster ovary cells. Oncogene 2009; 28: 2231-2237.
81. Chen BP, Uematsu N, Kobayashi J, Lerenthal Y, Krempler A, Yajima H et al. Ataxia telangiectasia mutated (ATM) is essential for DNA-PKcs phosphorylations at the Thr-2609 cluster upon DNA double strand break. J Biol Chem 2007; 282: 6582-6587.
82. Lavin MF, Kozlov S. DNA damage-induced signalling in ataxia-telangiectasia and related syndromes. Radiother Oncol 2007; 83: 231-237.
83. McEllin B, Camacho CV, Mukherjee B, Hahm B, Tomimatsu N, Bachoo RM et al. PTEN loss compromises homologous recombination repair in astrocytes: implications for glioblastoma therapy with temozolomide or poly(ADP-ribose) polymerase inhibitors. Cancer Res 2010; 70: 5457-5464.
84. Han B, Mehra R, Lonigro RJ, Wang L, Suleman K. Fluorescence in situ hybridization study shows association of PTEN deletion with ERG rearrangement during prostate cancer progression. Mod Pathol 2009; 22: 1083-1093.
85. Mendes-Pereira AM, Martin SA, Brough R, McCarthy A, Taylor JR, Kim JS et al. Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors. EMBO Mol Med 2009; 1: 315-322.
86. Clegg NJ, Couto SS, Wongvipat J, Hieronymus H, Carver BS. MYC cooperates with AKT in prostate tumorigenesis and alters sensitivity to mTOR inhibitors. PLoS ONE 2011; 6: e17449.
87. Liyanage M, Weaver Z, Barlow C, Coleman A, Pankratz DG, Anderson S et al. Abnormal rearrangement within the alpha/delta T-cell receptor locus in lymphomas from Atm-deficient mice. Blood 2000; 96: 1940-1946.
88. Korz C, Pscherer A, Benner A, Mertens D, Schaffner C, Leupolt E et al. Evidence for distinct pathomechanisms in B-cell chronic lymphocytic leukemia and mantle cell lymphoma by quantitative expression analysis of cell cycle and apoptosisassociated genes. Blood 2002; 99: 4554-4561.
89. Pusapati RV, Rounbehler RJ, Hong S, Powers JT, Yan M, Kiguchi K et al. ATM promotes apoptosis and suppresses tumorigenesis in response to Myc. Proc Natl Acad Sci USA 2006; 103: 1446-1451.
90. Guerra L, Albihn A, Tronnersjö S, Yan Q, Guidi R, Stenerlöw B et al. Myc is required for activation of the ATM-dependent checkpoints in response to DNA damage. PLoS One 2010; 5: e8924.
91. Murga M, Campaner S, Lopez-Contreras AJ, Toledo LI, Soria R, Montana MF et al. Exploiting oncogene induced replicative stress for the selective killing of Mycdriven tumors. Nat Struct Mol Biol 2011; 18: 1331-1335.
92. Hoglund A, Nilsson LM, Muralidharan SV, Hasvold LA, Merta P, Rudelius M et al. Therapeutic implications for the induced levels of Chk1 in Myc-expressing cancer cells. Clin Cancer Res 2011; 17: 7067-7079.
93. Gilad O, Nabet BY, Ragland RL, Schoppy DW, Smith KD, Durham AC et al. Combining ATR suppression with oncogenic Ras synergistically increases genomic instability, causing synthetic lethality or tumorigenesis in a dosagedependent manner. Cancer Res 2010; 70: 9693-9702.
94. Clark J, Attard G, Jhavar S, Flohr P, Reid A, De-Bono J et al. Complex patterns of ETS gene alteration arise during cancer development in the human prostate. Oncogene 2008; 27: 1993-2003.
95. Mosquera JM, Perner S, Genega EM, Sanda M, Hofer MD, Mertz KD et al. Characterization of TMPRSS2-ERG fusion high-grade prostatic intraepithelial neoplasia and potential clinical implications. Clin Cancer Res 2008; 14: 3380-3385.
96. Tomlins SA, Laxman B, Varambally S, Cao X, Yu J et al. Role of the TMPRSS2-ERG Gene Fusion in Prostate Cancer. Neoplasia 2008; 10: 177-188.
97. Wang J, Cai Y, Ren C, Ittmann M. Expression of variant TMPRSS2/ERG fusion messenger RNAs is associated with aggressive prostate cancer. Cancer Res 2006; 66: 8347-8351.
98. Tomlins SA, Rhodes DR, Perner S, Dhanasekaran SM, Mehra R, Sun XW et al. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science 2005; 310: 644-648.
99. Brenner JC, Ateeq B, Li Y, Yocum AK, Cao Q, Asangani IA et al. Mechanistic rationale for inhibition of poly(ADP-ribose) polymerase in ETS gene fusionpositive prostate cancer. Cancer Cell 2011; 19: 664-678.
100. Chatterjee P, Choudhary GS, Sharma A, Singh K, Heston WD, Ciezki J et al. PARP inhibition sensitizes to low dose-rate radiation TMPRSS2-ERG fusion geneexpressing and PTEN-deficient prostate cancer cells. PLoS ONE 2013; 8: e60408.
101. Sandhu SK, Schelman WR, Wilding G, Moreno V, Baird RD, Miranda S 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: 882-892.
102. Schiewer MJ, Goodwin JF, Han S, Brenner JC, Augello M. A, Dean JL et al. Dual roles of PARP-1 promote cancer growth and progression. Cancer Discov 2012; 2: 1134-1149.
103. Al-Ubaidi FL, Schultz N, Loseva O, Egevad L, Granfors T, Helleday T. Castration therapy results in decreased Ku70 levels in prostate cancer. Clin Cancer Res 2013; 19: 1547-1556.
104. Thacker J. The RAD51 gene family, genetic instability and cancer. Cancer Lett 2005; 219: 125-135.
105. Likun L, Chang W, Yang G, Ren C, Park S, Karantanos T et al. Targeting poly(ADPribose) polymerase and the c-myb-regulated DNA damage response pathway in castration-resistant prostate cancer. Sci Signal 2014; 7: ra47.
106. Aparicio AM, Harzstark AL, Corn PG, Wen S, Araujo JC, Tu SM et al. Platinumbased chemotherapy for variant castrate-resistant prostate cancer. Clin Cancer Res 2013; 19: 3621-3630.