Unique functions of CHK1 and WEE1 underlie synergistic anti-tumor activity upon pharmacologic inhibition

Cancer Cell International

Volumn 12, Issue , 2012, Pages

  Guertin, Amy D ^a   Martin, Melissa M ^b   Roberts, Brian ^c   Hurd, Melissa ^a   Qu, Xianlu ^a   Miselis, Nathan R ^a   Liu, Yaping ^a   Li, Jing ^a   Feldman, Igor ^a   Benita, Yair ^a   Bloecher, Andrew ^a   Toniatti, Carlo ^d   Shumway, Stuart D ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

^b AMGEN INC   (United States)

^c HUDSONALPHA INSTITUTE FOR BIOTECHNOLOGY   (United States)

^d Applied Management Sciences Institute   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; CHECKPOINT KINASE 1; CYCLIN DEPENDENT KINASE; MK 1775; MK 8776; PROTEIN KINASE; PROTEIN P53; UNCLASSIFIED DRUG; WEE1 PROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL; CELL CYCLE S PHASE; CONTROLLED STUDY; DNA DAMAGE; DNA REPLICATION; DRUG POTENTIATION; ENZYME ACTIVITY; FEMALE; HUMAN; HUMAN CELL; MOUSE; NONHUMAN; TUMOR XENOGRAFT;

EID: 84868654250     PISSN: None     EISSN: 14752867     Source Type: Journal    
DOI: 10.1186/1475-2867-12-45     Document Type: Article

References (36)

1. Carrassa L, Damia G. Unleashing Chk1 in cancer therapy. Cell Cycle 2011, 10:2121-2128. 10.4161/cc.10.13.16398, 21610326.
2. Ma CX, Janetka JW, Piwnica-Worms H. Death by releasing the breaks: CHK1 inhibitors as cancer therapeutics. Trends Mol Med 2011, 17:88-96. 10.1016/j.molmed.2010.10.009, 21087899.
3. Daud A, Pringett GM, Mendelson DS, Munster PN, Goldman JW, Strosberg JR, et al. A phase I dose-escalation study of SCH 900776, a selective inhibitor of checkpoint kinase 1 (CHK1), in combination with gemcitabine (Gem) in subjects with advanced solid tumors (2010 ASCO Annual Meeting). J Clin Oncol 2010, 28:15s, 010. (suppl; abstr 3064).
4. Schellens JHM, Shapiro G, Pavlick AC, Tibes R, Leijen S, Tolaney SM, et al. Update on a phase I pharmacologic and pharmacodynamic study of MK-1775, a Wee1 tyrosine kinase inhibitor, in monotherapy and combination with gemcitabine, cisplatin, or carboplatin in patients with advanced solid tumors (2011 ASCO Annual Meeting). J Clin Oncol 2011, 29. 2011 (suppl; abstr 3068).
5. Zhao H, Watkins JL, Piwnica-Worms H. Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G(2) checkpoints. Proc Natl Acad Sci USA 2002, 99:14795-14800. 10.1073/pnas.182557299, 137498, 12399544.
6. Sorensen CS, Syluasen RG, Falck J, Schroeder T, Ronnstrand L, Khanna KK, et al. Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A. Cancer Cell 2003, 3:247-258. 10.1016/S1535-6108(03)00048-5, 12676583.
7. Sanchez Y, Wong C, Thoma RS, Richman R, Wu RQ, Piwnicaworms H, et al. 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.
8. OConnell MJ, Raleigh JM, Verkade HM, Nurse P. Chk1 is a wee1 kinase in the G(2) DNA damage checkpoint inhibiting cdc2 by Y15 phosphorylation. EMBO J 1997, 16:545-554. 10.1093/emboj/16.3.545, 1169658, 9034337.
9. Liu QH, Guntuku S, Cui XS, Matsuoka S, Cortez D, Tamai K, et al. 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. Petermann E, Maya-Mendoza A, Zachos G, Gillespie DAF, Jackson DA, Caldecott KW. Chk1 requirement for high global rates of replication fork progression during normal vertebrate S phase. Mol Cell Biol 2006, 26:3319-3326. 10.1128/MCB.26.8.3319-3326.2006, 1446959, 16581803.
11. Feijoo C, Hall-Jackson C, Wu R, Jenkins D, Leitch J, Gilbert DM, et al. Activation of mammalian Chk1 during DNA replication arrest: a role for Chk1 in the intra-S phase checkpoint monitoring replication origin firing. J Cell Biol 2001, 154:913-923. 10.1083/jcb.200104099, 1255922,1255922, 11535615.
12. Petermann E, Woodcock M, Helleday T. Chk1 promotes replication fork progression by controlling replication initiation. Proc Natl Acad Sci USA 2010, 107:16090-16095. 10.1073/pnas.1005031107, 2941317, 20805465.
13. Sorensen CS, Hansen LT, Dziegielewski J, Syljuasen RG, Lundin C, Bartek J, et al. The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair. Nat Cell Biol 2005, 7:195-U121. 10.1038/ncb1212, 15665856.
14. Hu BC, Wang HY, Wang X, Lu HR, Huang CF, Powell SN, et al. Fhit and CHK1 have opposing effects on homologous recombination repair. Cancer Res 2005, 65:8613-8616. 10.1158/0008-5472.CAN-05-1966, 16204026.
15. Kramer A, Mailand N, Lukas C, Syljuasen RG, Wilkinson CJ, Nigg EA, et al. Centrosome-associated Chk1 prevents premature activation of cyclin-B-Cdk1 kinase. Nat Cell Biol 2004, 6:884-U71. 10.1038/ncb1165, 15311285.
16. Lam MH, Liu QH, Elledge SJ, Rosen JM. Chk1 is haploinsufficient for multiple functions critical to tumor suppression. Canc Cell 2004, 6:45-59.
17. Tominaga Y, Li C, Wang R-H, Deng C-X. Murine Wee1 Plays a Critical Role in Cell Cycle Regulation and Pre-Implantation Stages of Embryonic Development. Int J Biol Sci 2006, 2:161-170. 1483124, 16810330.
18. Raleigh JM, O'Connell MJ. The G(2) DNA damage checkpoint targets both Wee1 and Cdc25. J Cell Sci 2000, 113:1727-1736.
19. Beck H, Nahse V, Larsen MSY, Groth P, Clancy T, Lees M, et al. Regulators of cyclin-dependent kinases are crucial for maintaining genome integrity in S phase. J Cell Biol 2010, 188:629-638. 10.1083/jcb.200905059, 2835936, 20194642.
20. Dominguez-Kelly R, Martin Y, Koundrioukoff S, Tanenbaum ME, Smits VAJ, Medema RH, et al. Wee1 controls genomic stability during replication by regulating the Mus81-Eme1 endonuclease. J Cell Biol 2011, 194:567-579. 10.1083/jcb.201101047, 3160579, 21859861.
21. Bridges KA, Hirai H, Buser CA, Brooks C, Liu HF, Buchholz TA, et al. MK-1775, a Novel Wee1 Kinase Inhibitor, Radiosensitizes p53-Defective Human Tumor Cells. Clin Cancer Res 2011, 17:5638-5648. 10.1158/1078-0432.CCR-11-0650, 3167033, 21799033.
22. PosthumaDeBoer J, Wurdinger T, Graat HCA, Van Beusechem VW, Helder MN, Van Royen BJ, et al. WEE1 inhibition sensitizes osteosarcoma to radiotherapy. BMC Cancer 2011, 11:156. 10.1186/1471-2407-11-156, 3103478, 21529352.
23. Rajeshkumar NV, De Oliveira E, Ottenhof N, Watters J, Brooks D, Demuth T, et al. MK-1775, a Potent Wee1 Inhibitor, Synergizes with Gemcitabine to Achieve Tumor Regressions, Selectively in p53-Deficient Pancreatic Cancer Xenografts. Clin Cancer Res 2011, 17:2799-2806. 10.1158/1078-0432.CCR-10-2580, 3307341, 21389100.
24. Mir SE, Hamer PCD, Krawczyk PM, Balaj L, Claes A, Niers JM, et al. In Silico Analysis of Kinase Expression Identifies WEE1 as a Gatekeeper against Mitotic Catastrophe in Glioblastoma. Canc Cell 2010, 18:244-257.
25. Hirai H, Arai T, Okada M, Nishibata T, Kobayashi M, Sakai N, et al. MK-1775, a small molecule Wee1 inhibitor, enhances antitumor efficacy of various DNA-damaging agents, including 5-fluorouracil. Canc Biol Ther 2010, 9:514-522.
26. Hirai H, Iwasawa Y, Okada M, Arai T, Nishibata T, Kobayashi M, et al. Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents. Mol Cancer Ther 2009, 8:2992-3000. 10.1158/1535-7163.MCT-09-0463, 19887545.
27. Murrow LM, Garimella SV, Jones TL, Caplen NJ, Lipkowitz S. Identification of WEE1 as a potential molecular target in cancer cells by RNAi screening of the human tyrosine kinome. Breast Canc Res Treat 2010, 122:347-357.
28. Iorns E, Lord CJ, Grigoriadis A, McDonald S, Fenwick K, Mackay A, et al. Integrated Functional, Gene Expression and Genomic Analysis for the Identification of Cancer Targets. PLoS One 2009, 4(4):e5120. 10.1371/journal.pone.0005120, 2663812, 19357772.
29. Parry D, Guzi T, Shanahan F, Davis N, Prabhavalkar D, Wiswell D, et al. Dinaciclib (SCH 727965), a Novel and Potent Cyclin-Dependent Kinase Inhibitor. Mol Cancer Ther 2010, 9:2344-2353. 10.1158/1535-7163.MCT-10-0324, 20663931.
30. Davies KD, Humphries MJ, Sullivan FX, von Carlowitz I, Le Huerou Y, Mohr PJ, et al. Single-Agent Inhibition of Chk1 Is Antiproliferative in Human Cancer Cell Lines In Vitro and Inhibits Tumor Xenograft Growth In Vivo. Oncol Res 2011, 19:349-363. 10.3727/096504011X13079697132961, 21936404.
31. Hamer PCD, Mir SE, Noske D, Van Noorden CJF, Wurdinger T. WEE1 Kinase Targeting Combined with DNA-Damaging Cancer Therapy Catalyzes Mitotic Catastrophe. Clin Cancer Res 2011, 17:4200-4207. 10.1158/1078-0432.CCR-10-2537, 21562035.
32. Xiao Z, Xue J, Gu WZ, Bui M, Li GQ, Tao ZF, et al. Cyclin B1 is an efficacy-predicting biomarker for Chk1 inhibitors. Biomarkers 2008, 13:579-596. 10.1080/13547500802063240, 18671143.
33. Davies KD, Cable PL, Garrus JE, Sullivan FX, von Carlowitz I, Huerou YL, et al. Chk1 inhibition and Wee1 inhibition combine synergistically to impede cellular proliferation. Canc Biol Ther 2011, 12:1-9.
34. Carrassa L, Chila R, Lupi M, Ricci F, Celenza C, Mazzoletti M, et al. Combined inhibition of Chk1 and Wee1 In vitro synergistic effect translates to tumor growth inhibition in vivo. Cell Cycle 2012, 11:2507-2517. 10.4161/cc.20899, 22713237.
35. Guzi TJ, Paruch K, Dwyer MP, Labroli M, Shanahan F, Davis N, et al. Targeting the Replication Checkpoint Using SCH 900776, a Potent and Functionally Selective CHK1 Inhibitor Identified via High Content Screening. Mol Cancer Ther 2011, 10:591-602. 10.1158/1535-7163.MCT-10-0928, 21321066.
36. Bliss CI. The toxicity of poisons applied jointly. Ann Appl Biol 1939, 26:585-615.