Opportunities for translation: Targeting DNA repair pathways in pancreatic cancer

Biochimica et Biophysica Acta - Reviews on Cancer

Volumn 1846, Issue 1, 2014, Pages 45-54

  Maginn, Elaina N ^a   de Sousa, Camila H ^a   Wasan, Harpreet S ^a   Stronach, Euan A ^a  

^a HAMMERSMITH HOSPITAL   (United Kingdom)

Author keywords

Chemoresistance; DNA damage response and repair; DNA damaging agents; Pancreatic ductal adenocarcinoma

Indexed keywords

BRCA2 PROTEIN; CARBOPLATIN; CISPLATIN; DNA TOPOISOMERASE INHIBITOR; DOXORUBICIN; ETOPOSIDE; FLUOROURACIL; GEMCITABINE; IRINOTECAN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; OXALIPLATIN; PLATINUM COMPLEX; TOPOTECAN; XRCC3 PROTEIN; ANTINEOPLASTIC AGENT; DNA; FOLINIC ACID; PLATINUM DERIVATIVE;

ADVANCED CANCER; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; BINDING AFFINITY; CATALYSIS; CELL DIVISION; CELL SURVIVAL; DNA DAMAGE; DNA END JOINING REPAIR; DNA REPAIR; DNA REPLICATION; DNA SYNTHESIS; DNA TRANSCRIPTION; DRUG EFFICACY; DRUG SAFETY; ENZYME RECONSTITUTION; EXCISION REPAIR; GENE TARGETING; GENETIC POLYMORPHISM; GENETIC TRANSCRIPTION AND TRANSLATION; HOMOLOGOUS RECOMBINATION; HUMAN; IMMUNOMODULATION; MISMATCH REPAIR; ONCOGENE; OUTCOME ASSESSMENT; PANCREAS ADENOCARCINOMA; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PROTEIN BINDING; REVIEW; SIGNAL TRANSDUCTION; TRANSLATIONAL RESEARCH; CANCER CHEMOTHERAPY; CANCER MORTALITY; CANCER PROGNOSIS; CELL DEATH; CHROMOSOME ABERRATION; COPY NUMBER VARIATION; DNA STRUCTURE; GENETIC HETEROGENEITY;

CHEMORESISTANCE; DNA DAMAGE RESPONSE AND REPAIR; DNA DAMAGING AGENTS; PANCREATIC DUCTAL ADENOCARCINOMA;

ANIMALS; ANTINEOPLASTIC AGENTS; CARCINOMA, PANCREATIC DUCTAL; DNA COPY NUMBER VARIATIONS; DNA DAMAGE; DNA REPAIR; HUMANS; MOLECULAR TARGETED THERAPY; PANCREATIC NEOPLASMS; SIGNAL TRANSDUCTION; TRANSLATIONAL MEDICAL RESEARCH;

EID: 84899048388     PISSN: 0304419X     EISSN: 18792561     Source Type: Journal    
DOI: 10.1016/j.bbcan.2014.04.002     Document Type: Review

References (170)

1. http://www.cancerresearchuk.org/cancer-info/cancerstats/.
2. Hidalgo M. Pancreatic cancer. N. Engl. J. Med. 2010, 362(17):1605-1617.
3. Vincent A., Herman J., Schulick R., et al. Pancreatic cancer. Lancet 2011, 378(9791):607-620.
4. Gillen S., Schuster T., Meyer Zum Büschenfelde C., et al. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med. 2010, 7(4):e1000267.
5. Seufferlein T., Bachet J.B., Van Cutsem E., et al. Pancreatic adenocarcinoma: ESMO-ESDO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol. 2012, 23(Suppl. 7):vii33-vii40.
6. Tempero M.A., Arnoletti J.P., Behrman S.W., et al. Pancreatic adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines. J. Natl. Compr. Cancer Netw. 2012, 10(6):703-713.
7. Hruban R.H., Adsay N.V., Albores-Saavedra J., et al. Intraepithelial neoplasia: a new nomenclature and classification system for pancreatic duct lesions. Am. J. Surg. Pathol. 2011, 25:579-586.
8. Bosetti C., Lucenteforte E., Silverman D.T., et al. Cigarette smoking and pancreatic cancer: an analysis from the International Pancreatic Cancer Case-Control Consortium (Panc4). Ann. Oncol. 2012, 23(7):1880-1888.
9. Ben Q., Xu M., Ning X., et al. Diabetes mellitus and risk of pancreatic cancer: a meta-analysis of cohort studies. Eur. J. Cancer 2011, 47(13):1928-1937.
10. Li D., Tang H., Hassan M.M., et al. Diabetes and risk of pancreatic cancer: a pooled analysis of three large case-control studies. Cancer Causes Control 2011, 22(2):189-197.
11. Raimondi S., Maisonneuve P., Lowenfels A.B. Epidemiology of pancreatic cancer: an overview. Nat. Rev. Gastroenterol. Hepatol. 2009, 6(12):699-708.
12. Feldmann G., Beaty R., Hruban R.H., et al. Molecular genetics of pancreatic intraepithelial neoplasia. J. Hepatobiliary Pancreat. Surg. 2007, 14(3):224-232.
13. Jones S., Zhang X., Parsons D.W., et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008, 321(5897):1801-1806.
14. Cowley M.J., Chang D.K., Pajic M., et al. Understanding pancreatic cancer genomes. J. Hepatobiliary Pancreat. Sci. 2013, 20(6):549-556.
15. Ruiz C., Lenkiewicz E., Evers L., et al. Advancing a clinically relevant perspective of the clonal nature of cancer. Proc. Natl. Acad. Sci. U. S. A. 2011, 108(29):12054-12059.
16. Biankin A.V., Waddell N., Kassahn K.S., et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature 2012, 491(7424):399-405.
17. Custodio A., Puente J., Sastre J., et al. Second-line therapy for advanced pancreatic cancer: a review of the literature and future directions. Cancer Treat. Rev. 2009, 35(8):676-684.
18. Stathis A., Moore M.J. Advanced pancreatic carcinoma: current treatment and future challenges. Nat. Rev. Clin. Oncol. 2010, 7:163-172.
19. Michl P., Gress T.M. Current concepts and novel targets in advanced pancreatic cancer. Gut 2012, 62(2):317-326.
20. Conroy T., Desseigne F., Ychou M., et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N. Engl. J. Med. 2011, 364(19):1817-1825.
21. Saif M.W., Chabot J. Chemotherapy: metastatic pancreatic cancer - is FOLFIRINOX the new standard?. Nat. Rev. Clin. Oncol. 2011, 8(8):452-453.
22. Ma W.W., Hidalgo M. The winning FORMULA-tion: the development of paclitaxel in pancreatic cancer. Clin. Cancer Res. 2013, 19(20):5572-5579.
23. Von Hoff D.D., Ervin T., Arena F.P., et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N. Engl. J. Med. 2013, 369(18):1691-1703.
24. Hosein P.J., de Lima Lopes G., Pastorini V.H., et al. A phase II trial of nab-Paclitaxel as second-line therapy in patients with advanced pancreatic cancer. Am. J. Clin. Oncol. 2013, 36(2):151-156.
25. Zhang D.S., Wang D.S., Wang Z.Q., et al. Phase I/II study of albumin-bound nab-paclitaxel plus gemcitabine administered to Chinese patients with advanced pancreatic cancer. Cancer Chemother. Pharmacol. 2013, 71(4):1065-1072.
26. Jiricny J. The multifaceted mismatch-repair system. Nat. Rev. Mol. Cell Biol. 2006, 7:335-346.
27. Caldecott K.W. Single-strand break repair and genetic disease. Nat. Rev. Genet. 2008, 9:619-631.
28. Lieber M.R. The mechanism of human nonhomologous DNA end joining. J. Biol. Chem. 2008, 283(1):1-5.
29. Cleaver J.E., Lam E.T., Revet I. Disorders of nucleotide excision repair: the genetic and molecular basis of heterogeneity. Nat. Rev. Genet. 2009, 10(11):756-768.
30. Moynahan M.E., Jasin M. Mitotic homologous recombination maintains genomic stability and suppresses tumorigenesis. Nat. Rev. Mol. Cell Biol. 2010, 11(3):196-207.
31. Kennedy R.D., D'Andrea A.D. DNA repair pathways in clinical practice: lessons from pediatric cancer susceptibility syndromes. J. Clin. Oncol. 2006, 24(23):3799-3808.
32. Al-Ejeh F., Kumar R., Wiegmans A., et al. Harnessing the complexity of DNA-damage response pathways to improve cancer treatment outcomes. Oncogene 2010, 29(46):6085-6098.
33. Bouwman P., Jonkers J. The effects of deregulated DNA damage signalling on cancer chemotherapy response and resistance. Nat. Rev. Cancer 2012, 12(9):587-598.
34. Lord C.J., Ashworth A. The DNA damage response and cancer therapy. Nature 2012, 481(7381):287-294.
35. McWilliams R.R., Bamlet W.R., Cunningham J.M., et al. Polymorphisms in DNA repair genes, smoking, and pancreatic adenocarcinoma risk. Cancer Res. 2008, 68(12):4928-4935.
36. Okazaki T., Jiao L., Chang P., et al. Single-nucleotide polymorphisms of DNA damage response genes are associated with overall survival in patients with pancreatic cancer. Clin. Cancer Res. 2008, 14(7):2042-2048.
37. Giovannetti E., Pacetti P., Reni M., et al. Association between DNA-repair polymorphisms and survival in pancreatic cancer patients treated with combination chemotherapy. Pharmacogenomics 2011, 12(12):1641-1652.
38. Innocenti F., Owzar K., Cox N.L., et al. A genome-wide association study of overall survival in pancreatic cancer patients treated with gemcitabine in CALGB 80303. Clin. Cancer Res. 2012, 18(2):577-584.
39. El-Khamisy S.F., Masutani M., Suzuki H., et al. A requirement for PARP-1 for the assembly or stability of XRCC1 nuclear foci at sites of oxidative DNA damage. Nucleic Acids Res. 2003, 31:5526-5533.
40. Schreiber V., Dantzer F., Ame J.C., et al. Poly(ADP-ribose): novel functions for an old molecule. Nat. Rev. Mol. Cell Biol. 2006, 7(7):517-528.
41. Ciccia A., Elledge S.J. The DNA damage response: making it safe to play with knives. Mol. Cell 2010, 40(2):179-204.
42. 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(2):137-146.
43. Curtin N.J., Szabo C. Therapeutic application of PARP inhibitors: anticancer therapy and beyond. Mol. Aspects Med. 2013, 34(6):1217-1256.
44. Bryant H.E., Schultz N., Thomas H.D., et al. Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 2005, 434:913-917.
45. Farmer H., McCabe N., Lord C.J., et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 2005, 434:917-921.
46. Hahn S.A., Greenhalf B., Ellis I., et al. BRCA2 germline mutations in familial pancreatic carcinoma. J. Natl. Cancer Inst. 2003, 95(3):214-221.
47. Iqbal J., Ragone A., Lubinski J., et al. The incidence of pancreatic cancer in BRCA1 and BRCA2 mutation carriers. Br. J. Cancer 2012, 107(12):2005-2009.
48. Stadler Z.K., Salo-Mullen E., Patil S.M., et al. Prevalence of BRCA1 and BRCA2 mutations in Ashkenazi Jewish families with breast and pancreatic cancer. Cancer 2012, 118(2):493-499.
49. Lucas A.L., Shakya R., Lipsyc M.D., et al. High prevalence of BRCA1 and BRCA2 germline mutations with loss of heterozygosity in a series of resected pancreatic adenocarcinoma and other neoplastic lesions. Clin. Cancer Res. 2013, 19(13):3396-3403.
50. Huang L., Wu C., Yu D., et al. Identification of common variants in BRCA2 and MAP2K4 for susceptibility to sporadic pancreatic cancer. Carcinogenesis 2013, 34(5):1001-1005.
51. Jones S., Hruban R.H., Kamiyama M., et al. Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science 2009, 324(5924):217.
52. Burris H.A., Moore M.J., Andersen J., et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J. Clin. Oncol. 1997, 15(6):2403-2413.
53. Mini E., Nobili S., Caciagli B., et al. Cellular pharmacology of gemcitabine. Ann. Oncol. 2006, 17(Suppl. 5):v7-v12.
54. Giovannetti E., Mey V., Nannizzi S., et al. Pharmacogenetics of anticancer drug sensitivity in pancreatic cancer. Mol. Cancer Ther. 2006, 5(6):1387-1395.
55. van Moorsel C.J., Pinedo H.M., Veerman G., et al. Mechanisms of synergism between cisplatin and gemcitabine in ovarian and non-small-cell lung cancer cell lines. Br. J. Cancer 1999, 80(7):981-990.
56. Peters G.J., Van Moorsel C.J., Lakerveld B., et al. Effects of gemcitabine on cis-platinum-DNA adduct formation and repair in a panel of gemcitabine and cisplatin-sensitive or -resistant human ovarian cancer cell lines. Int. J. Oncol. 2006, 28(1):237-244.
57. Agarwal R., Kaye S.B. Ovarian cancer: strategies for overcoming resistance to chemotherapy. Nat. Rev. Cancer 2003, 3(7):502-516.
58. Bernstein C., Bernstein H., Payne C.M., et al. DNA repair/pro-apoptotic dual-role proteins in five major DNA repair pathways: fail-safe protection against carcinogenesis. Mutat. Res. 2002, 511(2):145-178.
59. Bergman A.M., Ruiz van Haperen V.W., Veerman G., et al. Synergistic interaction between cisplatin and gemcitabine in vitro. Clin. Cancer Res. 1996, 2(3):521-530.
60. Yang L.Y., Li L., Jiang H., et al. Expression of ERCC1 antisense RNA abrogates gemicitabine-mediated cytotoxic synergism with cisplatin in human colon tumor cells defective in mismatch repair but proficient in nucleotide excision repair. Clin. Cancer Res. 2000, 6:773-781.
61. Crul M., van Waardenburg R.C., Bocxe S., et al. DNA repair mechanisms involved in gemcitabine cytotoxicity and in the interaction between gemcitabine and cisplatin. Biochem. Pharmacol. 2003, 65:275-282.
62. Moufarij M.A., Phillips D.R., Cullinane C. Gemcitabine potentiates cisplatin cytotoxicity and inhibits repair of cisplatin-DNA damage in ovarian cancer cell lines. Mol. Pharmacol. 2003, 63:862-869.
63. Ledermann J.A., Gabra H., Jayson G.C., et al. Inhibition of carboplatin-induced DNA interstrand cross-link repair by gemcitabine in patients receiving these drugs for platinum-resistant ovarian cancer. Clin. Cancer Res. 2010, 16(19):4899-4905.
64. Smith J.A., Gaikwad A., Ramondetta L.M., et al. Determination of the mechanism of gemcitabine modulation of cisplatin drug resistance in panel of human endometrial cancer cell lines. Gynecol. Oncol. 2006, 103(2):518-522.
65. Martin L.P., Hamilton T.C., Schilder R.J. Platinum resistance: the role of DNA repair pathways. Clin. Cancer Res. 2008, 14(5):1291-1295.
66. Ceppi P., Volante M., Novello S., et al. ERCC1 and RRM1 gene expressions but not EGFR are predictive of shorter survival in advanced non-small-cell lung cancer treated with cisplatin and gemcitabine. Ann. Oncol. 2006, 17(12):1818-1825.
67. Holm B., Mellemgaard A., Skov T., Skov B.G. Different impact of excision repair cross-complementation group 1 on survival in male and female patients with inoperable non-small-cell lung cancer treated with carboplatin and gemcitabine. J. Clin. Oncol. 2009, 27(26):4254-4259.
68. Lee H.W., Choi Y.W., Han J.H., et al. Expression of excision repair cross-complementation group 1 protein predicts poor outcome in advanced non-small cell lung cancer patients treated with platinum-based doublet chemotherapy. Lung Cancer 2009, 65(3):377-382.
69. Reynolds C., Obasaju C., Schell M.J., et al. Randomized phase III trial of gemcitabine-based chemotherapy with in situ RRM1 and ERCC1 protein levels for response prediction in non-small-cell lung cancer. J. Clin. Oncol. 2009, 27(34):5808-5815.
70. Vilmar A.C., Santoni-Rugiu E., Sørensen J.B. ERCC1 and histopathology in advanced NSCLC patients randomized in a large multicenter phase III trial. Ann. Oncol. 2010, 21(9):1817-1824.
71. Joerger M., deJong D., Burylo A., et al. Tubulin, BRCA1, ERCC1, Abraxas, RAP80 mRNA expression, p53/p21 immunohistochemistry and clinical outcome in patients with advanced non small-cell lung cancer receiving first-line platinum-gemcitabine chemotherapy. Lung Cancer 2011, 74(2):310-317.
72. Liao W.Y., Shih J.Y., Chang G.C., et al. Genetic polymorphism of XRCC1 Arg399Gln is associated with survival in non-small-cell lung cancer patients treated with gemcitabine/platinum. J. Thorac. Oncol. 2012, 7(6):973-981.
73. Zhang G.B., Chen J., Wang L.R., et al. RRM1 and ERCC1 expression in peripheral blood versus tumor tissue in gemcitabine/carboplatin-treated advanced non-small cell lung cancer. Cancer Chemother. Pharmacol. 2012, 69(5):1277-1287.
74. Welsh C., Day R., McGurk C., et al. Reduced levels of XPA, ERCC1 and XPF DNA repair proteins in testis tumor cell lines. Int. J. Cancer 2004, 110(3):352-361.
75. Usanova S., Piée-Staffa A., Sied U., et al. Cisplatin sensitivity of testis tumour cells is due to deficiency in interstrand-crosslink repair and low ERCC1-XPF expression. Mol. Cancer 2010, 9:248.
76. Mendoza J., Martínez J., Hernández C., et al. Association between ERCC1 and XPA expression and polymorphisms and the response to cisplatin in testicular germ cell tumours. Br. J. Cancer 2013, 109(1):68-75.
77. Rosell R., Crino L., Danenberg K., et al. Targeted therapy in combination with gemcitabine in non-small cell lung cancer. Semin. Oncol. 2003, 30(4 Suppl. 10):19-25.
78. Chew H.K., Doroshow J.H., Frankel P., et al. Phase II studies of gemcitabine and cisplatin in heavily and minimally pretreated metastatic breast cancer. J. Clin. Oncol. 2009, 27(13):2163-2169.
79. Kim S.H., Lee G.W., Lee M.J., et al. Clinical significance of ERCC2 haplotype-tagging single nucleotide polymorphisms in patients with unresectable non-small cell lung cancer treated with first-line platinum-based chemotherapy. Lung Cancer 2012, 77(3):578-584.
80. Ren S., Zhou S., Wu F., et al. Association between polymorphisms of DNA repair genes and survival of advanced NSCLC patients treated with platinum-based chemotherapy. Lung Cancer 2012, 75(1):102-109.
81. Avan A., Pacetti P., Reni M., et al. Prognostic factors in gemcitabine-cisplatin polychemotherapy regimens in pancreatic cancer: XPD-Lys751Gln polymorphism strikes back. Int. J. Cancer 2013, 133(4):1016-1022.
82. Maithel S.K., Coban I., Kneuertz P.J., et al. Differential expression of ERCC1 in pancreas adenocarcinoma: high tumor expression is associated with earlier recurrence and shortened survival after resection. Ann. Surg. Oncol. 2011, 18(9):2699-2705.
83. Akita H., Zheng Z., Takeda Y., et al. Significance of RRM1 and ERCC1 expression in resectable pancreatic adenocarcinoma. Oncogene 2009, 8(32):2903-2909.
84. Valsecchi M.E., Holdbrook T., Leiby B.E., et al. Is there a role for the quantification of RRM1 and ERCC1 expression in pancreatic ductal adenocarcinoma?. BMC Cancer 2012, 12:104-114.
85. Kamikozuru H., Kuramochi H., Hayashi K., et al. ERCC1 codon 118 polymorphism is a useful prognostic marker in patients with pancreatic cancer treated with platinum-based chemotherapy. Int. J. Oncol. 2008, 32(5):1091-1096.
86. Mancuso A., Sacchetta S., Saletti P.C., et al. Clinical and molecular determinants of survival in pancreatic cancer patients treated with second-line chemotherapy: results of an Italian/Swiss multicenter survey. Anticancer Res. 2010, 30(10):4289-4295.
87. de las Peñas R., Sanchez-Ronco M., Alberola V., et al. Polymorphisms in DNA repair genes modulate survival in cisplatin/gemcitabine-treated non-small-cell lung cancer patients. Ann. Oncol. 2006, 17(4):668-675.
88. Li D., Liu H., Jiao L., et al. Significant effect of homologous recombination DNA repair gene polymorphisms on pancreatic cancer survival. Cancer Res. 2006, 66(6):3323-3330.
89. Prevo R., Fokas E., Reaper P.M., et al. The novel ATR inhibitor VE-821 increases sensitivity of pancreatic cancer cells to radiation and chemotherapy. Cancer Biol. Ther. 2012, 13(11):1072-1081.
90. Engelke C.G., Parsels L.A., Qian Y., et al. Sensitization of pancreatic cancer to chemoradiation by the Chk1 Inhibitor MK8776. Clin. Cancer Res. 2013, 19(16):4412-4421.
91. Ma C.X., Janetka J.W., Piwnica-Worms H. Death by releasing the breaks: CHK1 inhibitors as cancer therapeutics. Trends Mol. Med. 2011, 17(2):88-96.
92. Porcelli L., Quatrale A.E., Mantuano P., et al. Optimize radiochemotherapy in pancreatic cancer: PARP inhibitors a new therapeutic opportunity. Mol. Oncol. 2013, 7(3):308-322.
93. Hill R., Lee P.W. The DNA-dependent protein kinase (DNA-PK): more than just a case of making ends meet?. Cell Cycle 2010, 9(17):3460-3469.
94. Stronach E.A., Chen M., Maginn E.N., et al. DNA-PK mediates AKT activation and apoptosis inhibition in clinically acquired platinum resistance. Neoplasia 2011, 13(11):1069-1080.
95. Couch F.J., Johnson M.R., Rabe K.G., et al. The prevalence of BRCA2 mutations in familial pancreatic cancer. Cancer Epidemiol. Biomarkers Prev. 2007, 16(2):342-346.
96. Ferrone C.R., Levine D.A., Tang L.H., et al. BRCA germline mutations in Jewish patients with pancreatic adenocarcinoma. J. Clin. Oncol. 2009, 27:433-438.
97. Fogelman D.R., Wolff R.A., Kopetz S., et al. Evidence for the efficacy of Iniparib, a PARP-1 inhibitor, in BRCA2-associated pancreatic cancer. Anticancer Res. 2011, 31(4):1417-1420.
98. Lowery M.A., Kelsen D.P., Stadler Z.K., et al. An emerging entity: pancreatic adenocarcinoma associated with a known BRCA mutation: clinical descriptors, treatment implications, and future directions. Oncologist 2011, 16(10):1397-1402.
99. Edwards S.L., Brough R., Lord C.J., et al. Resistance to therapy caused by intragenic deletion in BRCA2. Nature 2008, 451(7183):1111-1115.
100. Gallmeier E., Kern S.E. Absence of specific cell killing of the BRCA2-deficient human cancer cell line CAPAN1 by poly(ADP-ribose) polymerase inhibition. Cancer Biol. Ther. 2005, 4(7):703-706.
101. Jacob D.A., Bahra M., Langrehr J.M., et al. Combination therapy of poly (ADP-ribose) polymerase inhibitor 3-aminobenzamide and gemcitabine shows strong antitumor activity in pancreatic cancer cells. J. Gastroenterol. Hepatol. 2007, 22(5):738-748.
102. Hirai T., Shirai H., Fujimori H., et al. Radiosensitization effect of poly(ADP-ribose) polymerase inhibition in cells exposed to low and high liner energy transfer radiation. Cancer Sci. 2012, 103(6):1045-1050.
103. Drew Y., Mulligan E.A., Vong W.T., et al. Therapeutic potential of poly(ADP-ribose) polymerase inhibitor AG014699 in human cancers with mutated or methylated BRCA1 or BRCA2. J. Natl. Cancer Inst. 2011, 103(4):334-346.
104. McCabe N., Lord C.J., Tutt A.N., et al. BRCA2-deficient CAPAN-1 cells are extremely sensitive to the inhibition of poly (ADP-ribose) polymerase: an issue of potency. Cancer Biol. Ther. 2005, 4(9):934-936.
105. Beger C., Ramadani M., Meyer S., et al. Down-regulation of BRCA1 in chronic pancreatitis and sporadic pancreatic adenocarcinoma. Clin. Cancer Res. 2004, 10(11):3780-3787.
106. Al-Sukhni W., Rothenmund H., Borgida A.E., et al. Germline BRCA1 mutations predispose to pancreatic adenocarcinoma. Hum. Genet. 2008, 124(3):271-278.
107. Wang T., Wentz S.C., Ausborn N.L., et al. Pattern of breast cancer susceptibility gene 1 expression is a potential prognostic biomarker in resectable pancreatic ductal adenocarcinoma. Pancreas 2013, 42(6):977-982.
108. Buisson R., Dion-CÔté A.M., Coulombe Y., et al. Cooperation of breast cancer proteins PALB2 and piccolo BRCA2 in stimulating homologous recombination. Nat. Struct. Mol. Biol. 2010, 17(10):1247-1254.
109. Gilardini Montani M.S., Prodosmo A., Stagni V., et al. ATM-depletion in breast cancer cells confers sensitivity to PARP inhibition. J. Exp. Clin. Cancer Res. 2013, 32(1):95-105.
110. Ihnen M., zu Eulenburg C., Kolarova T., et al. Therapeutic potential of the poly(ADP-ribose) polymerase inhibitor rucaparib for the treatment of sporadic human ovarian cancer. Mol. Cancer Ther. 2013, 12(6):1002-1015.
111. Williamson C.T., Kubota E., Hamill J.D., et al. Enhanced cytotoxicity of PARP inhibition in mantle cell lymphoma harbouring mutations in both ATM and p53. EMBO Mol. Med. 2012, 4(6):515-527.
112. Patel A.G., Sarkaria J.N., Kaufmann S.H. 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(8):3406-3411.
113. Morgan M.A., Parsels L.A., Zhao L., et al. Mechanism of radiosensitization by the Chk1/2 inhibitor AZD7762 involves abrogation of the G2 checkpoint and inhibition of homologous recombinational DNA repair. Cancer Res. 2010, 70(12):4972-4981.
114. Vance S., Liu E., Zhao L., Parsels J.D., et al. Selective radiosensitization of p53 mutant pancreatic cancer cells by combined inhibition of Chk1 and PARP1. Cell Cycle 2011, 10(24):4321-4329.
115. Fokas E., Prevo R., Hammond E.M., et al. Targeting ATR in DNA damage response and cancer therapeutics. Cancer Treat. Rev. 2014, 40(1):109-117.
116. Piao L., Nakagawa H., Ueda K., et al. C12orf48, termed PARP-1 binding protein, enhances poly(ADP-ribose) polymerase-1 (PARP-1) activity and protects pancreatic cancer cells from DNA damage. Genes Chromosom. Cancer 2011, 50(1):13-24.
117. Moldovan G.L., Dejsuphong D., Petalcorin M.I., et al. Inhibition of homologous recombination by the PCNA-interacting protein PARI. Mol. Cell 2012, 45(1):75-86.
118. O'Connor K.W., Dejsuphong D., Park E., et al. PARI overexpression promotes genomic instability and pancreatic tumorigenesis. Cancer Res. 2013, 73(8):2529-2539.
119. Klauschen F., von Winterfeld M., Stenzinger A., et al. High nuclear poly-(ADP-ribose)-polymerase expression is prognostic of improved survival in pancreatic cancer. Histopathology 2012, 61(3):409-416.
120. Chang D.T., Chapman C.H., Norton J.A., et al. Expression of p16(INK4A) but not hypoxia markers or poly adenosine diphosphate-ribose polymerase is associated with improved survival in patients with pancreatic adenocarcinoma. Cancer 2010, 116(22):5179-5187.
121. Riabinska A., Daheim M., Herter-Sprie G.S., et al. Therapeutic targeting of a robust non-oncogene addiction to PRDKC in ATM-defective tumours. Sci. Transl. Med. 2013, 5(189):189ra78.
122. Li Y.H., Wang X., Pan Y., et al. Inhibition of non-homologous end joining repair impairs pancreatic cancer growth and enhances radiation response. PLoS One 2012, 7(6):e39588.
123. Pommier Y. Drugging topoisomerases: lessons and challenges. ACS Chem. Biol. 2013, 8(1):82-95.
124. Wagener D.J., Verdonk H.E., Dirix L.Y., et al. Phase II trial of CPT-11 in patients with advanced pancreatic cancer, an EORTC early clinical trials group study. Ann. Oncol. 1995, 6(2):129-132.
125. Ueno H., Okusaka T., Funakoshi A., et al. A phase II study of weekly irinotecan as first-line therapy for patients with metastatic pancreatic cancer. Cancer Chemother. Pharmacol. 2007, 59:447-454.
126. Yi S.Y., Park Y.S., Kim H.S., et al. Irinotecan monotherapy as second-line treatment in advanced pancreatic cancer. Cancer Chemother. Pharmacol. 2009, 63(6):1141-1145.
127. Cui Y., Brosnan J.A., Blackford A.L., et al. Genetically defined subsets of human pancreatic cancer show unique in vitro chemosensitivity. Clin. Cancer Res. 2012, 18(23):6519-6530.
128. Sun W., Hewitt M.R., Theobald M.R., et al. A phase 1 study of fixed dose rate gemcitabine and irinotecan in patients with advanced pancreatic and biliary cancer. Cancer 2007, 110(12):2768-2774.
129. Neri B., Cipriani G., Grifoni R., et al. Gemcitabine plus irinotecan as first-line weekly therapy in locally advanced and/or metastatic pancreatic cancer. Oncol. Res. 2009, 17(11-12):559-564.
130. Lipton A., Campbell-Baird C., Witters L., et al. Phase II trial of gemcitabine, irinotecan, and celecoxib in patients with advanced pancreatic cancer. J. Clin. Gastroenterol. 2010, 44(4):286-288.
131. Pourquier P., Gioffre C., Kohlhagen G., et al. Gemcitabine (2',2'-difluoro-2'-deoxycytidine), an antimetabolite that poisons topoisomerase I. Clin. Cancer Res. 2002, 8(8):2499-2504.
132. Lawrie T.A., Rabbie R., Thoma C., et al. Pegylated liposomal doxorubicin for first-line treatment of epithelial ovarian cancer. Cochrane Database Syst. Rev. 2013, 10:CD010482.
133. Hansel D.E., Ashfaq R., Rahman A., et al. A subset of pancreatic adenocarcinomas demonstrates coamplification of topoisomerase IIalpha and HER2/neu: use of immunolabeling and multicolor FISH for potential patient screening andtreatment. Am. J. Clin. Pathol. 2005, 123(1):28-35.
134. Tsiambas E., Karameris A., Tiniakos D.G., et al. Evaluation of topoisomerase IIa expression in pancreatic ductal adenocarcinoma: a pilot study using chromogenic in situ hybridization and immunohistochemistry on tissue microarrays. Pancreatology 2007, 7(1):45-52.
135. Macdonald J.S., Jacobson J.L., Modiano M., et al. A phase II trial of etoposide, leucovorin, 5-FU, and interferon alpha 2b (ELFI)+G-CSF for patients with pancreatic adenocarcinoma: a Southwest Oncology Group study (SWOG 9413). Investig. New Drugs 2000, 18(3):269-273.
136. Reni M., Passoni P., Panucci M.G., et al. Definitive results of a phase II trial of cisplatin, epirubicin, continuous-infusion fluorouracil, and gemcitabine in stage IV pancreatic adenocarcinoma. J. Clin. Oncol. 2001, 19(10):2679-2686.
137. Reni M., Cordio S., Milandri C., et al. Gemcitabine versus cisplatin, epirubicin, fluorouracil, and gemcitabine in advanced pancreatic cancer: a randomised controlled multicentre phase III trial. Lancet Oncol. 2005, 6(6):369-376.
138. Melnik M.K., Webb C.P., Richardson P.J., et al. Phase II trial to evaluate gemcitabine and etoposide for locally advanced or metastatic pancreatic cancer. Mol. Cancer Ther. 2010, 9(8):2423-2429.
139. Mambrini A., Bassi C., Torri T., et al. Systemic gemcitabine and capecitabine plus intra-arterial epirubicin and cisplatin as second-line chemotherapy in gemcitabine-failure pancreatic cancer. Pancreas 2011, 40(6):983-984.
140. Lage H., Aki-Sener E., Yalcin I. High antineoplastic activity of new heterocyclic compounds in cancer cells with resistance against classical DNA topoisomerase II-targeting drugs. Int. J. Cancer 2006, 119(1):213-220.
141. Goodell J.R., Ougolkov A.V., Hiasa H., et al. Acridine-based agents with topoisomerase II activity inhibit pancreatic cancer cell proliferation and induce apoptosis. J. Med. Chem. 2008, 51(2):179-182.
142. Oppegard L.M., Ougolkov A.V., Luchini D.N., et al. Novel acridine-based compounds that exhibit an anti-pancreatic cancer activity are catalytic inhibitors of human topoisomerase II. Eur. J. Pharmacol. 2009, 602(2-3):223-229.
143. de Campos-Nebel M., Larripa I., Gonzalez-Cid M. Topoisomerase II-mediated DNA damage is differently repaired during the cell cycle by non-homologous end joining and homologous recombination. PLoS One 2010, 5(9). (pii:e12541).
144. Elguero M.E., de Campos-Nebel M., Gonzalez-Cid M. DNA-PKcs-dependent NHEJ pathway supports the progression of topoisomerase II poison-induced chromosome aberrant cells. Environ. Mol. Mutagen. 2012, 53(8):608-618.
145. Conradt L., Henrich A., Wirth M., et al. Mdm2 inhibitors synergize with topoisomerase II inhibitors to induce p53-independent pancreatic cancer cell death. Int. J. Cancer 2013, 132(10):2248-2257.
146. Bouska A., Eischen C.M. Mdm2 affects genome stability independent of p53. Cancer Res. 2009, 69(5):1697-1701.
147. Azmi A.S., Aboukameel A., Banerjee S., et al. MDM2 inhibitor MI-319 in combination with cisplatin is an effective treatment for pancreatic cancer independent of p53 function. Eur. J. Cancer 2010, 46(6):1122-1131.
148. Azmi A.S., Banerjee S., Ali S., et al. Network modeling of MDM2 inhibitor-oxaliplatin combination reveals biological synergy in wt-p53 solid tumors. Oncotarget 2011, 2(5):378-392.
149. Fritsche P., Seidler B., Schüler S., et al. HDAC2 mediates therapeutic resistance of pancreatic cancer cells via the BH3-only protein NOXA. Gut 2009, 58(10):1399-1409.
150. Zhang Y.W., Regairaz M., Seiler J.A., et al. Poly(ADP-ribose) polymerase and XPF-ERCC1 participate in distinct pathways for the repair of topoisomerase I-induced DNA damage in mammalian cells. Nucleic Acids Res. 2011, 39(9):3607-3620.
151. Yamanaka K., Sasagawa Y., Ogura T. Recent advances in p97/VCP/Cdc48 cellular functions. Biochim. Biophys. Acta 2012, 1823(1):130-137.
152. Laguë M.N., Romieu-Mourez R., Bonneil É., et al. Proteomic profiling of a mouse model for ovarian granulose cell tumor identifies VCP as a highly sensitive serum tumor marker in several human cancers. PLoS One 2012, 7(8):e42470.
153. Yamamoto S., Tomita Y., Nakamori S., et al. Elevated expression of valosin-containing protein (p97) in hepatocellular carcinoma is correlated with increased incidence of tumor recurrence. J. Clin. Oncol. 2003, 21:447-452.
154. Valle C.W., Min T., Bodas M., et al. Critical role of VCP/p97 in the pathogenesis and progression of non-small cell lung carcinoma. PLoS One 2011, 6(12):e29073.
155. Liu Y., Hei Y., Shu Q., et al. VCP/p97, down-regulated by microRNA-129-5p, could regulate the progression of hepatocellular carcinoma. PLoS One 2012, 7(4):e35800.
156. Hannah J., Zhou P. Regulation of DNA damage response pathways by the cullin-RING ubiquitin ligases. DNA Repair (Amst) 2009, 8(4):536-543.
157. Kerzendorfer C., Whibley A., Carpenter G., et al. Mutations in Cullin 4B result in a human syndrome associated with increased camptothecin-induced topoisomerase I-dependent DNA breaks. Hum. Mol. Genet. 2010, 19(7):1324-1334.
158. Huyen Y., Zgheib O., Ditullio R.A., et al. Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks. Nature 2004, 432(7015):406-411.
159. Barry E.R., Corry G.N., Rasmussen T.P. Targeting DOT1L action and interactions in leukemia: the role of DOT1L in transformation and development. Expert Opin. Ther. Targets 2010, 14(4):405-418.
160. Anglin J.L., Song Y. A medicinal chemistry perspective for targeting histone H3 lysine-79 methyltransferase DOT1L. J. Med. Chem. 2013, 56(22):8972-8983.
161. Damia G., Imperatori L., Stefanini M., D'Incalci M. Sensitivity of CHO mutant cell lines with specific defects in nucleotide excision repair to different anti-cancer agents. Int. J. Cancer 1996, 66(6):779-783.
162. Damia G., Guidi G., D'Incalci M. Expression of genes involved in nucleotide excision repair and sensitivity to cisplatin and melphalan in human cancer cell lines. Eur. J. Cancer 1998, 34(11):1783-1788.
163. Li W., Melton D.W. Cisplatin regulates the MAPK kinase pathway to induce increased expression of DNA repair gene ERCC1 and increase melanoma chemoresistance. Oncogene 2012, 31(19):2412-2422.
164. McNeil E.M., Melton D.W. DNA repair endonuclease ERCC1-XPF as a novel therapeutic target to overcome chemoresistance in cancer therapy. Nucleic Acids Res. 2012, 40(20):9990-10004.
165. Unsal-Kaçmaz K., Chastain P.D., Qu P.P., et al. The human Tim/Tipin complex coordinates an intra-S checkpoint response to UV that slows replication fork displacement. Mol. Cell. Biol. 2007, 27(8):3131-3142.
166. Urtishak K.A., Smith K.D., Chanoux R.A., et al. Timeless maintains genomic stability and suppresses sister chromatid exchange during unperturbed DNA replication. J. Biol. Chem. 2009, 284(13):8777-8785.
167. Smith K.D., Fu M.A., Brown E.J. Tim-Tipin dysfunction creates an indispensible reliance on the ATR-Chk1 pathway for continued DNA synthesis. J. Cell Biol. 2009, 187(1):15-23.
168. Yang X., Wood P.A., Hrushesky W.J. Mammalian TIMELESS is required for ATM-dependent CHK2 activation and G2/M checkpoint control. J. Biol. Chem. 2010, 285(5):3030-3034.
169. Yoshida K., Sato M., Hase T., et al. TIMELESS is overexpressed in lung cancer and its expression correlates with poor patient survival. Cancer Sci. 2013, 104(2):171-177.
170. Relles D., Sendecki J., Chipitsyna G., et al. Circadian gene expression and clinicopathologic correlates in pancreatic cancer. J. Gastrointest. Surg. 2013, 17(3):443-450.