Synthetic lethal RNAi screening identifies sensitizing targets for gemcitabine therapy in pancreatic cancer

Journal of Translational Medicine

Volumn 7, Issue , 2009, Pages

  Azorsa, David O ^a   Gonzales, Irma M ^a   Basu, Gargi D ^a   Choudhary, Ashish ^a   Arora, Shilpi ^a   Bisanz, Kristen M ^a   Kiefer, Jeffrey A ^a   Henderson, Meredith C ^a   Trent, Jeffrey M ^a   Von Hoff, Daniel D ^a   Mousses, Spyro ^a  

^a TRANSLATIONAL GENOMICS RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHECKPOINT KINASE 1; CHECKPOINT KINASE 2; GEMCITABINE; PD 407824; PROTEIN SERINE THREONINE KINASE INHIBITOR; SB 218078; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; ALKALOID; ANTINEOPLASTIC ANTIMETABOLITE; CARBAZOLE DERIVATIVE; DEOXYCYTIDINE; DRUG DERIVATIVE; ENZYME INHIBITOR; PROTEIN KINASE;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL; CONTROLLED STUDY; DRUG RESPONSE; DRUG SENSITIZATION; DRUG TARGETING; GENE IDENTIFICATION; GENE LIBRARY; GENE SILENCING; GENE TARGETING; GENETIC SCREENING; HIGH THROUGHPUT SCREENING; HUMAN; HUMAN CELL; PANCREAS CANCER; RNA INTERFERENCE; RNA SYNTHESIS; AGED; CELL SURVIVAL; DOSE RESPONSE; DRUG EFFECT; FEMALE; GENETIC TRANSFECTION; GENETICS; IMPEDANCE; MALE; METABOLISM; MIDDLE AGED; PANCREAS TUMOR; REPRODUCIBILITY; TUMOR CELL LINE;

AGED; ALKALOIDS; ANTIMETABOLITES, ANTINEOPLASTIC; CARBAZOLES; CELL LINE, TUMOR; CELL SURVIVAL; DEOXYCYTIDINE; DOSE-RESPONSE RELATIONSHIP, DRUG; ELECTRIC IMPEDANCE; ENZYME INHIBITORS; FEMALE; GENE SILENCING; HUMANS; MALE; MIDDLE AGED; PANCREATIC NEOPLASMS; PROTEIN KINASES; REPRODUCIBILITY OF RESULTS; RNA INTERFERENCE; RNA, SMALL INTERFERING; TRANSFECTION;

EID: 67650085633     PISSN: None     EISSN: 14795876     Source Type: Journal    
DOI: 10.1186/1479-5876-7-43     Document Type: Article

References (53)

1. Jemal A Siegel R Ward E Hao Y Xu J Murray T Thun MJ Cancer statistics, 2008 CA Cancer J Clin 2008, 58:71-96 10.3322/CA.2007.0010 18287387
2. Carmichael J Fink U Russell RC Spittle MF Harris AL Spiessi G Blatter J Phase II study of gemcitabine in patients with advanced pancreatic cancer Br J Cancer 1996, 73:101-105 8554969
3. Burris HA 3rd Moore MJ Andersen J Green MR Rothenberg ML Modiano MR Cripps MC Portenoy RK Storniolo AM Tarassoff P Nelson R Dorr FA Stephens CD Von Hoff DD 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, 15:2403-2413 9196156
4. Lawrence TS Chang EY Hahn TM Hertel LW Shewach DS Radiosensitization of pancreatic cancer cells by 2′,2′-difluoro-2′-deoxycytidine Int J Radiat Oncol Biol Phys 1996, 34:867-872 8598364
5. Bepler G Sommers KE Cantor A Li X Sharma A Williams C Chiappori A Haura E Antonia S Tanvetyanon T Simon G Obasaju C Robinson LA Clinical efficacy and predictive molecular markers of neoadjuvant gemcitabine and pemetrexed in resectable non-small cell lung cancer J Thorac Oncol 2008, 3:1112-1118 10.1097/JTO.0b013e3181874936 18827606
6. Richardson DL Backes FJ Seamon LG Zanagnolo V O'Malley DM Cohn DE Fowler JM Copeland LJ Combination gemcitabine, platinum, and bevacizumab for the treatment of recurrent ovarian cancer Gynecol Oncol 2008, 11:461-466 10.1016/j.ygyno.2008.08.011
7. Moulder S Valkov N Neuger A Choi J Lee JH Minton S Munster P Gump J Lacevic M Lush R Sullivan D Phase 2 study of gemcitabine and irinotecan in metastatic breast cancer with correlatives to determine topoisomerase I localization as a predictor of response Cancer 2008, 113:2646-2654 10.1002/cncr.23916 18823053
8. Vulfovich M Rocha-Lima C Novel advances in pancreatic cancer treatment Expert Rev Anticancer Ther 2008, 8:993-1002 10.1586/14737140.8.6.993 18533808
9. Nencioni A Sandy P Dillon C Kissler S Blume-Jensen P Van Parijs L RNA interference for the identification of disease-associated genes Curr Opin Mol Ther 2004, 6:136-140 15195924
10. Aza-Blanc P Cooper CL Wagner K Batalov S Deveraux QL Cooke MP Identification of modulators of TRAIL-induced apoptosis via RNAi-based phenotypic screening Mol Cell 2003, 12:627-637 10.1016/ S1097-2765(03)00348-4 14527409
11. Azorsa DOMS Caplen NJ Gene silencing through RNA interference: Potential for therapeutics and functional genomics Letters in Peptide Research 2004, 10:361-372 10.1007/BF02484571
12. Bartz SR Zhang Z Burchard J Imakura M Martin M Palmieri A Needham R Guo J Gordon M Chung N Warrener P Jackson AL Carleton M Locco L Santini F Smith T Kunapuli P Ferrer M Strulovici B Friend SH Linsley PS Small interfering RNA screens reveal enhanced cisplatin cytotoxicity in tumor cells having both BRCA network and TP53 disruptions Mol Cell Biol 2006, 26:9377-9386 1698535 17000754 10.1128/MCB.01229-06
13. Lu J Ruhf ML Perrimon N Leder P A genome-wide RNA interference screen identifies putative chromatin regulators essential for E2F repression Proc Natl Acad Sci USA 2007, 104:9381-9386 1890503 17517653 10.1073/ pnas.0610279104
14. MacKeigan JP Murphy LO Blenis J Sensitized RNAi screen of human kinases and phosphatases identifies new regulators of apoptosis and chemoresistance Nat Cell Biol 2005, 7:591-600 10.1038/ncb1258 15864305
15. Root DE Hacohen N Hahn WC Lander ES Sabatini DM Genome-scale loss-of-function screening with a lentiviral RNAi library Nat Methods 2006, 3:715-719 10.1038/nmeth924 16929317
16. Sepp KJ Hong P Lizarraga SB Liu JS Mejia LA Walsh CA Perrimon N Identification of neural outgrowth genes using genome-wide RNAi PLoS Genet 2008, 4:e1000111 2435276 18604272 10.1371/journal.pgen.1000111
17. Whitehurst AW Bodemann BO Cardenas J Ferguson D Girard L Peyton M Minna JD Michnoff C Hao W Roth MG Xie XJ White MA Synthetic lethal screen identification of chemosensitizer loci in cancer cells Nature 2007, 446:815-819 10.1038/nature05697 17429401
18. Yunis AA Arimura GK Russin DJ Human pancreatic carcinoma (MIA PaCa-2) in continuous culture: Sensitivity to asparaginase Int J Cancer 1977, 19:128-135 10.1002/ijc.2910190118 832918
19. Arora S Wang Y Jia Z Vardar-Sengul S Munawar A Doctor KS Birrer M McClelland M Adamson E Mercola D Egr1 regulates the coordinated expression of numerous EGF receptor target genes as identified by ChIP-on-chip Genome Biol 2008, 9:R166 2614498 19032775 10.1186/ gb-2008-9-11-r166
20. Azorsa DO Cunliffe HE Meltzer PS Association of steroid receptor coactivator AIB1 with estrogen receptor-alpha in breast cancer cells Breast Cancer Res Treat 2001, 70:89-101 10.1023/A:1012972808558 11768608
21. Solly K Wang X Xu X Strulovici B Zheng W Application of real-time cell electronic sensing (RT-CES) technology to cell-based assays Assay Drug Dev Technol 2004, 2:363-372 10.1089/adt.2004.2.363 15357917
22. Rodriguez-Mora OG Lahair MM Evans MJ Kovacs CJ Allison RR Sibata CH White KS McCubrey JA Franklin RA Inhibition of the CaM-kinases augments cell death in response to oxygen radicals and oxygen radical inducing cancer therapies in MCF-7 human breast cancer cells Cancer Biol Ther 2006, 5:1022-1030 16855386
23. Ewart-Toland A Briassouli P de Koning JP Mao JH Yuan J Chan F MacCarthy-Morrogh L Ponder BA Nagase H Burn J Ball S Almeida M Linardopoulos S Balmain A Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human Nat Genet 2003, 34:403-412 10.1038/ng1220 12881723
24. Hafner C Schmitz G Meyer S Bataille F Hau P Langmann T Dietmaier W Landthaler M Vogt T Differential gene expression of Eph receptors and ephrins in benign human tissues and cancers Clin Chem 2004, 50:490-499 10.1373/clinchem.2003.026849 14726470
25. McAllister RA Fixter LM Campbell EH The effect of tumour growth on liver pantothenate, CoA, and fatty acid synthetase activity in the mouse Br J Cancer 1988, 57:83-86 2831928
26. Spano JP Chodkiewicz C Maurel J Wong R Wasan H Barone C Letourneau R Bajetta E Pithavala Y Bycott P Trask P Laiu K Ricart AD Kim S Rixe O Efficacy of gemcitabine plus axitinib compared with gemcitabine alone in patients with advanced pancreatic cancer: An open-label randomised phase II study Lancet 2008, 371:2101-2108 10.1016/S0140-6736(08)60661-3 18514303
27. Reni M Cordio S Milandri C Passoni P Bonetto E Oliani C Luppi G Nicoletti R Galli L Bordonaro R Passardi A Zerbi A Balzano G Aldrighetti L Staudacher C Villa E Di Carlo V Gemcitabine versus cisplatin, epirubicin, fluorouracil, and gemcitabine in advanced pancreatic cancer: a randomised controlled multicentre phase III trial Lancet Oncol 2005, 6:369-376 10.1016/S1470-2045(05)70175-3 15925814
28. Burris H 3rd Rocha-Lima C New therapeutic directions for advanced pancreatic cancer: Targeting the epidermal growth factor and vascular endothelial growth factor pathways Oncologist 2008, 13:289-298 10.1634/ theoncologist.2007-0134 18378539
29. Warner SL Munoz RM Stafford P Koller E Hurley LH Von Hoff DD Han H Comparing Aurora A and Aurora B as molecular targets for growth inhibition of pancreatic cancer cells Mol Cancer Ther 2006, 5:2450-2458 10.1158/1535-7163.MCT-06-0202 17041088
30. Hata T Furukawa T Sunamura M Egawa S Motoi F Ohmura N Marumoto T Saya H Horii A RNA interference targeting aurora kinase a suppresses tumor growth and enhances the taxane chemosensitivity in human pancreatic cancer cells Cancer Res 2005, 65:2899-2905 10.1158/0008-5472.CAN-04-3981 15805292
31. Okazaki T Jiao L Chang P Evans DB Abbruzzese JL Li D Single-nucleotide polymorphisms of DNA damage response genes are associated with overall survival in patients with pancreatic cancer Clin Cancer Res 2008, 14:2042-2048 2423806 18381943 10.1158/1078-0432.CCR-07-1520
32. Franklin RA Rodriguez-Mora OG Lahair MM McCubrey JA Activation of the calcium/calmodulin-dependent protein kinases as a consequence of oxidative stress Antioxid Redox Signal 2006, 8:1807-1817 10.1089/ ars.2006.8.1807 16987033
33. Abraham RT Cell cycle checkpoint signaling through the ATM and ATR kinases Genes Dev 2001, 15:2177-2196 10.1101/gad.914401 11544175
34. Wang Y Decker SJ Sebolt-Leopold J Knockdown of Chk1, Wee1 and Myt1 by RNA interference abrogates G2 checkpoint and induces apoptosis Cancer Biol Ther 2004, 3:305-313 14726685
35. Tang J Erikson RL Liu X Checkpoint kinase 1 (Chk1) is required for mitotic progression through negative regulation of polo-like kinase 1 (Plk1) Proc Natl Acad Sci USA 2006, 103:11964-11969 1567681 16873548 10.1073/pnas.0604987103
36. Sanchez Y Wong C Thoma RS Richman R Wu Z Piwnica-Worms H Elledge SJ Conservation of the Chk1 checkpoint pathway in mammals: Linkage of DNA damage to Cdk regulation through Cdc25 Science 1997, 277:1497-1501 10.1126/science.277.5331.1497 9278511
37. Liu Q Guntuku S Cui XS Matsuoka S Cortez D Tamai K Luo G Carattini-Rivera S DeMayo F Bradley A Donehower LA Elledge SJ Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint Genes Dev 2000, 14:1448-1459 316686 10859164 10.1101/gad.840500
38. Zhao H Watkins JL Piwnica-Worms H Disruption of the checkpoint kinase 1/ cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints Proc Natl Acad Sci USA 2002, 99:14795-14800 137498 12399544 10.1073/pnas.182557299
39. Morgan MA Parsels LA Parsels JD Mesiwala AK Maybaum J Lawrence TS Role of checkpoint kinase 1 in preventing premature mitosis in response to gemcitabine Cancer Res 2005, 65:6835-6842 10.1158/0008-5472.CAN-04-2246 16061666
40. Karnitz LM Flatten KS Wagner JM Loegering D Hackbarth JS Arlander SJ Vroman BT Thomas MB Baek YU Hopkins KM Lieberman HB CHen J Cliby WA Kaufmann SH Gemcitabine-induced activation of checkpoint signaling pathways that affect tumor cell survival Mol Pharmacol 2005, 68:1636-1644 16126823
41. O'Connor MJ Martin NM Smith GC Targeted cancer therapies based on the inhibition of DNA strand break repair Oncogene 2007, 26:7816-7824 10.1038/sj.onc.1210879 18066095
42. Shao RG Cao CX Shimizu T O'Connor PM Kohn KW Pommier Y Abrogation of an S-phase checkpoint and potentiation of camptothecin cytotoxicity by 7-hydroxystaurosporine (UCN-01) in human cancer cell lines, possibly influenced by p53 function Cancer Res 1997, 57:4029-4035 9307289
43. Parsels LA Morgan MA Tanska DM Parsels JD Palmer BD Booth RJ Denny WA Canman CE Kraker AJ Lawrence TS Maybaum J Gemcitabine sensitization by checkpoint kinase 1 inhibition correlates with inhibition of a Rad51 DNA damage response in pancreatic cancer cells Mol Cancer Ther 2009, 8:45-54 10.1158/1535-7163.MCT-08-0662 19139112
44. Giroux V Iovanna J Dagorn JC Probing the human kinome for kinases involved in pancreatic cancer cell survival and gemcitabine resistance Faseb J 2006, 20:1982-1991 10.1096/fj.06-6239com 17012250
45. Garber K New checkpoint blockers begin human trials J Natl Cancer Inst 2005, 97:1026-1028 16030295
46. Sha SK Sato T Kobayashi H Ishigaki M Yamamoto S Sato H Takada A Nakajyo S Mochizuki Y Friedman JM Cheng FC Okura T Kimura R Kufe DW Vonhoff DD Kawabe T Cell cycle phenotype-based optimization of G2-abrogating peptides yields CBP501 with a unique mechanism of action at the G2 checkpoint Mol Cancer Ther 2007, 6:147-153 10.1158/1535-7163.MCT-06-0371 17237275
47. Matthews DJ Yakes FM Chen J Tadano M Bornheim L Clary DO Tai A Wagner JM Miller N Kim YD Robertson S Murry L Karnitz LM Pharmacological abrogation of S-phase checkpoint enhances the anti-tumor activity of gemcitabine in vivo Cell Cycle 2007, 6:104-110 17245119
48. Zabludoff SD Deng C Grondine MR Sheehy AM Ashwell S Caleb BL Green S Haye HR Horn CL Janetka JW Liu D Mouchet E Ready S ROsenthal JL Queva C Schwartz GK Taylor KJ Tse AN Walker GE White AM AZD7762, a novel checkpoint kinase inhibitor, drives checkpoint abrogation and potentiates DNA-targeted therapies Mol Cancer Ther 2008, 7:2955-2966 10.1158/1535-7163.MCT-08-0492 18790776
49. Hasvold LA Wang L Przytulinska M Xiao Z Chen Z Gu WZ Merta PJ Xue J Kovar P Zhang H Park C Sowin TJ ROsenberg SH Lin NH Investigation of novel 7,8-disubstituted-5,10-dihydro-dibenzo[b,e][1,4]diazepin-11-ones as potent Chk1 inhibitors Bioorg Med Chem Lett 2008, 18:2311-2315 10.1016/j.bmcl.2008.02.080 18358720
50. Tse AN Carvajal R Schwartz GK Targeting checkpoint kinase 1 in cancer therapeutics Clin Cancer Res 2007, 13:1955-1960 10.1158/ 1078-0432.CCR-06-2793 17404075
51. Solit DB Ivy SP Kopil C Sikorski R Morris MJ Slovin SF Kelly WK DeLaCruz A Curley T Heller G Larson S Schwartz L Egorin MJ Rosen N Scher HI Phase I trial of 17-allylamino-17-demethoxygeldanamycin in patients with advanced cancer Clin Cancer Res 2007, 13:1775-1782 10.1158/ 1078-0432.CCR-06-1863 17363532
52. Bagatell R Gore L Egorin MJ Ho R Heller G Boucher N Zuhowski EG Whitlock JA Hunger SP Narendran A Katzenstein HM Arceci RJ Boklan J Herzog CE Whitesell L Ivy SP Trippett TM Phase I pharmacokinetic and pharmacodynamic study of 17-N-allylamino-17-demethoxygeldanamycin in pediatric patients with recurrent or refractory solid tumors: A pediatric oncology experimental therapeutics investigators consortium study Clin Cancer Res 2007, 13:1783-1788 10.1158/1078-0432.CCR-06-1892 17363533
53. Blasina A Hallin J Chen E Arango ME Kraynov E Register J Grant S Ninkovic S Chen P Nichols T O'Connor P Anderes K Breaching the DNA damage checkpoint via PF-00477736, a novel small-molecule inhibitor of checkpoint kinase 1 Mol Cancer Ther 2008, 7:2394-2404 10.1158/ 1535-7163.MCT-07-2391 18723486