Prospects for the use of ATR inhibitors to treat cancer

Pharmaceuticals

Volumn 3, Issue 5, 2010, Pages 1311-1334

  Wagner, Jill M ^a   Kaufmann, Scott H ^a  

^a MAYO CLINIC   (United States)

Author keywords

ATM; ATR; Chemotherapy; Chk1; Replication checkpoint

Indexed keywords

2 (2 CHLORO 4 IODOANILINO) N CYCLOPROPYLMETHOXY 3,4 DIFLUOROBENZAMIDE; 4 [3 CHLORO 4 (2 PYRIDINYLMETHOXY)ANILINO] 3 CYANO 6 (4 DIMETHYLAMINOCROTONAMIDO) 7 ETHOXYQUINOLINE; 7 ETHYL 10 HYDROXYCAMPTOTHECIN; 7 HYDROXYSTAUROSPORINE; ALKYLATING AGENT; ANTINEOPLASTIC AGENT; ANTINEOPLASTIC ANTIMETABOLITE; ATM PROTEIN; ATR PROTEIN; CAMPTOTHECIN; CARBOPLATIN; CHECKPOINT KINASE 1; CISPLATIN; CYTARABINE; DNA TOPOISOMERASE INHIBITOR; ETOPOSIDE; FLUOROURACIL; FOLINIC ACID; GEMCITABINE; IRINOTECAN; MITOMYCIN C; OXALIPLATIN; PHOSPHATIDYLINOSITOL 3 KINASE; PLATINUM COMPLEX; PROTEIN SERINE THREONINE KINASE INHIBITOR; SCHIZANDRIN B; TEMOZOLOMIDE; TOPOTECAN; UNCLASSIFIED DRUG; UNINDEXED DRUG; XL 9844;

ACUTE LEUKEMIA; ANTINEOPLASTIC ACTIVITY; BLADDER CANCER; BREAST TUMOR; CANCER THERAPY; CLINICAL TRIAL; COLON CANCER; DIGESTIVE SYSTEM CANCER; DNA DAMAGE; DNA SEQUENCE; DOWN REGULATION; DRUG EFFECT; DRUG EFFICACY; DRUG MECHANISM; DRUG SENSITIZATION; DRUG USE; ENZYME ACTIVATION; ENZYME INHIBITION; ENZYME SUBSTRATE COMPLEX; HEAD AND NECK CANCER; HEMATOLOGIC DISEASE; HUMAN; LEUKEMIA; LUNG NON SMALL CELL CANCER; LUNG SMALL CELL CANCER; LYMPHOMA; NEOPLASM; NONHUMAN; OVARY CANCER; PANCREAS CANCER; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVIEW; SIGNAL TRANSDUCTION; SOLID TUMOR; STOMACH CANCER; TELOMERE; TESTIS CANCER;

EID: 77954938500     PISSN: None     EISSN: 14248247     Source Type: Journal    
DOI: 10.3390/ph3051311     Document Type: Review

References (114)

1. Zhou, B.B.; Elledge, S.J. The DNA damage response: putting checkpoints in perspective. Nature 2000, 408, 433-439.
2. Kastan, M.B.; Bartek, J. Cell-cycle checkpoints and cancer. Nature 2004, 432, 316-323.
3. Keith, C.T.; Schreiber, S.L. PIK-Related Kinases: DNA Repair, Recombination, and Cell Cycle Checkpoints. Science 1995, 270, 50-51.
4. Engelman, J.A.; Luo, J.; Cantley, L.C. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat. Rev. Genet. 2006, 7, 606-619.
5. Bosotti, R.; Isacchi, A.; Sonnhammer, E.L. FAT: a novel domain in PIK-related kinases. Trends Biochem. Sci. 2000, 25, 225-227.
6. Sibanda, B.L.; Chirgadze, D.Y.; Blundell, T.L. Crystal structure of DNA-PKcs reveals a large open-ring cradle comprised of HEAT repeats. Nature 2010, 463, 118-121.
7. Llorca, O.; Rivera-Calzada, A.; Grantham, J.; Willison, K.R. Electron microscopy and 3D reconstructions reveal that human ATM kinase uses an arm-like domain to clamp around doublestranded DNA. Oncogene 2003, 22, 3867-3874.
8. Chen, X.; Zhao, R.; Glick, G.G.; Cortez, D. Function of the ATR N-terminal domain revealed by an ATM/ATR chimera. Exp. Cell. Res. 2007, 313, 1667-1674.
9. Cimprich, K.; Cortez, D. ATR: an essential regulator of genome integrity. Nat. Rev. Mol. Cell Biol. 2008, 9, 616-627.
10. Zou, L.; Elledge, S.J. Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes. Science 2003, 300, 1542-1548.
11. Ball, H.L.; Ehrhardt, M.R.; Mordes, D.A.; Glick, G.G.; Chazin, W.J.; Cortez, D. Function of a conserved checkpoint recruitment domain in ATRIP proteins. Mol. Cell Biol. 2007, 27, 3367-3377.
12. Mordes, D.A.; Glick, G.G.; Zhao, R.; Cortez, D. TopBP1 activates ATR through ATRIP and a PIKK regulatory domain. Genes. Dev. 2008, 22, 1478-1489.
13. Itakura, E.; Umeda, K.; Sekoguchia, E.; Takata, H.; Ohsumib, M.; Matsuura, A. ATR-dependent phosphorylation of ATRIP in response to genotoxic stress. Biochem. Biophys. Res. Commun. 2004, 323, 1197-1202.
14. Myers, J.S.; Zhao, R.; Xu, X.; Ham, A.-JL; Cortez, D. Cyclin-dependent kinase 2 dependent phosphorylation of ATRIP regulates the G2-M checkpoint response to DNA damage. Cancer Res. 2007, 67, 6685-6690.
15. Venere, M.; Snyder, A.; Zgheib, O.; Halazonetis, T.D. Phosphorylation of ATR-interacting protein on Ser239 mediates an interaction with breast-ovarian cancer susceptibility 1 and checkpoint function. Cancer Res. 2007, 67, 6100-6105.
16. Abraham, R.T. Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes. Dev. 2001, 15, 2177-2196.
17. Kim, S.T.; Lim, D.S.; Canman, C.E.; Kastan, M.B. Substrate specificities and identification of putative substrates of ATM kinase family members. J. Biol. Chem. 1999, 274, 37538-37543.
18. Abraham, R.T. Cell Cycle Checkpoint Signaling Through the ATM and ATR Kinases. Genes. Dev. 2001, 15, 2177-2196.
19. Oakley, G.G.; Loberg, L.I.; Yao, J.; Risinger, M.A.; Yunker, R.L.; Zernik-Kobak, M.; Khanna, K.K.; Lavin, M.F.; Carty, M.P.; Dixon, K. UV-induced hyperphosphorylation of replication protein a depends on DNA replication and expression of ATM protein. Mol. Biol. Cell 2001, 12, 1199-1213.
20. Cortez, D.; Wang, Y.; Qin, J.; Elledge, S.J. Requirement of ATM-dependent phosphorylation of brca1 in the DNA damage response to double-strand breaks. Science 1999, 286, 1162-1166.
21. Brown, E.J.; Baltimore, D. ATR disruption leads to chromosomal fragmentation and early embryonic lethality. Genes. Dev. 2000, 14, 397-402.
22. O'Connell, M.; J.Cimprich, K.A. G2 damage checkpoints: what is the turn-on? J. Cell Sci. 2005, 118, 1-6.
23. Roos-Mattjus, P.; Vroman, B.T.; Burtelow, M.A.; Rauen, M.; Eapen, A.K.; Karnitz, L.M. Genotoxin-Induced Rad9-Hus1-Rad1 (9-1-1) Chromatin Association is an Early Checkpoint Signaling Event. J. Biol. Chem. 2002, 277, 43809-43812.
24. Zou, L.; Cortez, D.; Elledge, S.J. Regulation of ATR substrate selection by Rad17-dependent loading of Rad9 complexes onto chromatin. Genes Dev. 2002, 16, 198-208.
25. Ellison, V.; Stillman, B. Biochemical characterization of DNA damage checkpoint complexes: clamp loader and clamp complexes with specificity for 5' recessed DNA. PLoS Biol. 2003, 1, E33.
26. Delacroix, S.; Wagner, J.M.; Kobayashi, M.; Yamamoto, K.; Karnitz, L.M. The Rad9-Hus1Rad1 (9-1-1) clamp activates checkpoint signaling via TopBP1. Genes Dev. 2007, 21, 1472-1477.
27. Kumagai, A.; Lee, J.; Yoo, H.Y.; Dunphy, W.G. TopBP1 activates the ATR-ATRIP complex. Cell 2006, 124, 943-955.
28. Mordes, D.A.; Cortez, D. Activation of ATR and related PIKKs. Cell Cycle 2008, 7, 2809-2812.
29. Liu, Q.; Guntuku, S.; Cui, X.; Matsuoka, S.; Cortez, D.; Tamai, K.; Luo, G.; Carattini-Rivera, S.; DeMayo, F.; Bradley, A.; Donehower, L.A.; Elledge, S.J. 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.
30. Kumagai, A.; Dunphy, W.G. Claspin, a novel protein required for the activation of Chk1 during a DNA replication checkpoint response in Xenopus egg extracts. Mol. Cell 2000, 6, 839-849.
31. Mickle, K.L.; Oliva, A.; Huberman, J.A.; Leatherwood, J. Checkpoint effects and telomere amplification during DNA re-replication in fission yeast. BMC Mol. Biol. 2007, 8, 119.
32. Loegering, D.; Arlander, S.J.; Hackbarth, J.; Vroman, B.T.; Roos-Mattjus, P.; Hopkins, K.M.; Lieberman, H.B.; Karnitz, L.M.; Kaufmann, S.H. Rad9 protects cells from topoisomerase poison-induced cell death. J. Biol. Chem. 2004, 279, 18641-18647.
33. Flatten, K.; Dai, N.T.; Vroman, B.T.; Loegering, D.; Erlichman, C.; Karnitz, L.M.; Kaufmann, S.H. The role of checkpoint kinase 1 in sensitivity to topoisomerase I poisons. J. Biol. Chem. 2005, 280, 14349-14355.
34. Kemp, M.G.; Akan, Z.; Yilmaz, S.; Grillo, M.; Smith-Roe, S.L.; Kang, T.H.; Cordeiro-Stone, M.; Kaufmann, W.K.; Abraham, R.T.; Sancar, A.; Unsal-Kacmaz, K. Tipin-RPA interaction mediates Chk1 phosphorylation by ATR in response to genotoxic stress. J. Biol. Chem. 2010,
35. 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, 15-23.
36. Sorensen, C.S.; Syljuasen, R.G.; Falck, J.; Schroeder, T.; Rönnstrand, L.; Khanna, K.K.; Zhou, B.; Bartek, J.; Lukas, J. 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.
37. Sanchez, Y.; Wong, C.; Thoma, R.S.; Richman, R.; Wu, Z.; Piwnica-Worms, H.; Elledge, S.J. Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25. Science 1997, 277, 1497-1501.
38. Peng, C.Y.; Graves, P.R.; Thoma, R.S.; Wu, Z.; Shaw, A.S.; Piwnica-Worms, H. Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216. Science 1997, 277, 1501-1505.
39. Bartek, J.; Lukas, C.; Lukas, J. Checking on DNA damage in S phase. Nat. Rev. Mol. Cell Biol. 2004, 5, 792-804.
40. Shirahige, K.; Hori, Y.; Shiraishi, K.; Yamashita, M.; Takahashi, K.; Obuse, C.; Tsurimoto, T.;Yoshikawa, H. Regulation of DNA-replication origins during cell-cycle progression. Nature 1998, 395, 618-621.
41. Feijoo, C.; Hall-Jackson, C.; Wu, R.; Jenkins, D.; Leitch, J.; Gilbert, D.M.; Smythe, C. 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.
42. Heffernan, T.P.; Simpson, D.A.; Frank, A.R.; Heinloth, A.N.; Paules, R.S.; Cordeiro-Stone, M.; Kaufmann, W.K. An ATR- and Chk1-dependent S checkpoint inhibits replicon initiation following UVC-induced DNA damage. Mol. Cell Biol. 2002, 22, 8552-8561.
43. Unsal-Kacmaz, K.; Chastain, P.D.; Qu, P.; Minoo, P.; Cordeiro-Stone, M.; Sancar, A.; Kaufmann, W.K. The human Tim/Tipin complex coordinates an Intra-S checkpoint response to UV that slows replication fork displacement. Mol. Cell Biol. 2007, 27, 3131-3142.
44. Liu, E.; Lee, A.Y.; Chiba, T.; Olson, E.; Sun, P.; Wu, X. The ATR-mediated S phase checkpoint prevents rereplication in mammalian cells when licensing control is disrupted. J. Cell Biol. 2007, 179, 643-657.
45. Kastan, M.B.; Lim, D.S. The many substrates and functions of ATM. Nat. Rev. Mol. Cell. Biol.2000, 1, 179-186.
46. Vousden, K.H.; Lu, X. Live or let die: the cell's response to p53. Nat. Rev. Cancer 2002 2, 594-604.
47. Lowe, S.W.; Cepro, E.; Evan, G. Intrinsic tumour suppression. Nature 2004,
48. Cliby, W.A.; Roberts, C.J.; Cimprich, K.A.; Stringer, C.M.; Lamb, J.R.; Schreiber, S.L.; Friend, S.H. Overexpression of a kinase-inactive ATR protein causes sensitivity to DNA-damaging agents and defects in cell cycle checkpoints. Embo. J. 1998, 17, 159-169.
49. Ewald, B.; Sampath, D.; Plunkett, W. ATM and the Mre11-Rad50-Nbs1 complex respond to nucleoside analogue-induced stalled replication forks and contribute to drug resistance. Cancer Res. 2008, 68, 7947-7955.
50. Zhao, H.; Piwnica-Worms, H. ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1. Mol. Cell Biol. 2001, 21, 4129-4139.
51. Pichiorri, F.; Ishii, H.; Okumura, H.; Trapasso, F.; Wang, Y.; Huebner, K. Molecular parameters of genome instability: roles of fragile genes at common fragile sites. J. Cell Biochem. 2008, 104, 1525-1533.
52. Casper, A.M.; Nghiem, P.; Arlt, M.F.; Glover, T.W. ATR regulates fragile site stability. Cell 2002, 111, 779-789.
53. Durkin, S.G.; Arlt, M.F.; Howlett, N.G.; Glover, T.W. Depletion of CHK1, but not CHK2, induces chromosomal instability and breaks at common fragile sites. Oncogene 2006, 25, 4381-4388.
54. Entezam, A.; Usdin, K. ATR protects the genome against CGG.CCG-repeat expansion in Fragile X premutation mice. Nucleic Acids Res. 2008, 36, 1050-1056.
55. Cha, R.S.; Kleckner, N. ATR homolog Mec1 promotes fork progression, thus averting breaks in replication slow zones. Science 2002, 297, 602-606.
56. Lenzmeier, B.A.; Freudenreich, C.H. Trinucleotide repeat instability: A hairpin curve at the crossroads of replication, recombination, and repair. Cytogenet. Genome Res. 2003, 100, 7-24.
57. Lahiri, M. Gustafson, T.L. Majors, E.R. Freudenreich, C.H. Expanded CAG repeats activate the DNA damage checkpoint pathway. Mol. Cell 2004, 15, 287-293.
58. Khadaroo, B.; Teixeira, M.T.; Luciano, P.; Eckert-Boulet, N.; Germann, S.M.; Simon, M.N.;Gallina, I.; Abdallah, P.; Gilson, E.; Géli, V.; Lisby, M. The DNA damage response at eroded telomeres and tethering to the nuclear pore complex. Nat. Cell Biol. 2009, 11, 980-987.
59. d'Adda di Fagagna, F.; Reaper, P.M.; Clay-Farrace, L.; Fiegler, H.; Carr, P.; von Zglinicki, T.; Saretzki G.; Carter, N.P.; Jackson, S.P. A DNA damage checkpoint response in telomereinitiated senescence. Nature 2003, 426, 194-198.
60. Ritchie, K.B.; Mallory, J.C.; Petes, T.D. Interactions of TLC1 (which encodes the RNA subunit of telomerase), TEL1, and MEC1 in regulating telomere length in the yeast Saccharomyces cerevisiae. Mol. Cell Biol. 1999, 19, 6065-6075.
61. Francia, S.; Weiss, R.S.; Hande, M.P.; Freire, R.; di Fagagna, F.A. Telomere and telomerase modulation by the mammalian Rad9/Rad1/Hus1 DNA-damage-checkpoint complex. Curr. Biol. 2006, 16, 1551-1558.
62. Matsuoka, S.; Ballif, B.A.; Smogorzewska, A.; McDonald, E.R., III; Hurov, K.E.; Luo, J.; Bakalarski, C.E.; Zhao, Z.; Solimini, N.; Lerenthal, Y.; Shiloh, Y.; Gygi, S.P.; Elledge, S.J. ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 2007, 316, 1160-1166.
63. Shechter, D.; Costanzo, V.; Gautier, J. ATR and ATM regulate the timing of DNA replication origin firing. Nat. Cell Biol. 2004, 6, 648-655.
64. Maya-Mendoza, A.; Petermann, E.; Gillespie, D.A.F.; Caldecott, K.W.; Jackson, D.A. Chk1 regulates the density of active replication origins during the vertebrate S phase. Embo. J. 2007, 26, 2719-2731.
65. Brush, G.S.; Morrow, D.M.; Hieter, P.; Kelly, T.J. The ATM homologue MEC1 is required for phosphorylation of replication protein A in yeast. Proc. Natl. Acad. Sci. USA 1996,93, 15075-15080.
66. Liu, J.S.; Kuo, S.R.; Melendy, T. Phosphorylation of replication protein A by S-phase checkpoint kinases. DNA Repair (Amst) 2006, 5, 369-380.
67. Cortez, D.; Glick, G.; Elledge, S.J. Minichromosome maintenance proteins are direct targets of the ATM and ATR checkpoint kinases. Proc. Natl. Acad. Sci. USA 2004, 101, 10078-10083.
68. Yoo, H.Y.; Shevchenko, A.; Shevchenko, A.; Dunphy, W.G. Mcm2 is a direct substrate of ATM and ATR during DNA damage and DNA replication checkpoint responses. J. Biol. Chem. 2004, 279, 53353-53364.
69. Trenz, K.; Errico, A.; Costanzo, V. Plx1 is required for chromosomal DNA replication under stressful conditions. Embo J. 2008, 27, 876-885.
70. Chen, J. Ataxia telangiectasia-related protein is involved in the phosphorylation of BRCA1 following deoxyribonucleic acid damage. Cancer Res. 2000, 60, 5037-5039.
71. Pichierri, P.; Rosselli, F.; Franchitto, A. Werner's syndrome protein is phosphorylated in an ATR/ATM-dependent manner following replication arrest and DNA damage induced during the S phase of the cell cycle. Oncogene 2003, 22, 1491-1500.
72. Tripathi, V.; Kaur, S.; Sengupta, S. Phosphorylation-dependent interactions of BLM and 53BP1 are required for their anti-recombinogenic roles during homologous recombination. Carcinogenesis 2008, 29, 52-61.
73. Khakhar, R.R.; Cobb, J.A.; Bjergbaek, L.; Hickson, I.D.; Gasser, S.M. RecQ helicases: multiple roles in genome maintenance. Trends Cell Biol. 2003, 13, 493-501.
74. Bachrati, C.Z.; Borts, R.H.; Hickson, I.D. Mobile D-loops are a preferred substrate for the Bloom's syndrome helicase. Nucleic Acids Res. 2006, 34, 2269-2279.
75. Opresko, P.L.; Sowd, G.; Wang, H. The Werner syndrome helicase/exonuclease processes mobile D-loops through branch migration and degradation. PLoS One 2009, 4, e4825.
76. Ho, G.P.; Margossian, S.; Taniguchi, T.; D'Andrea; A.D. Phosphorylation of FANCD2 on two novel sites is required for mitomycin C resistance. Mol. Cell Biol. 2006, 26, 7005-7015.
77. Mukhopadhyay, U.K.; Senderowicz, A.M.; Ferbeyre, G. RNA silencing of checkpoint regulators sensitizes p53-defective prostate cancer cells to chemotherapy while sparing normal cells. Cancer Res. 2005, 65, 2872-2881.
78. Pan, Y.; Ren, K.H.; He, H.W.; Shao, R.G. Knockdown of Chk1 sensitizes human colon carcinoma HCT116 cells in a p53-dependent manner to lidamycin through abrogation of a G2/M checkpoint and induction of apoptosis. Cancer Biol. Ther. 2009, 8, 1559-1566.
79. Tao, Y.; Leteur, C.; Zhang, P.; Castedo, M.; Pierré, A.; Golsteyn, R.M.; Bourhis, J.; Kroemer, G.; Deutsch, E. Radiosensitization by Chir-124, a selective CHK1 inhibitor: Effects of p53 and cell cycle checkpoints. Cell Cycle 2009, 8, 1196-1205.
80. Powell, S.N.; DeFrank, J.S.; Connell, P.; Eogan, M.; Preffer, F.; Dombkowski, D.; Tang, W.; Friend, S. Differential sensitivity of p53(-) and p53(+) cells to caffeine-induced radiosensitization and override of G2 delay. Cancer Res. 1995, 55, 1643-1648.
81. Strunz, A.M.; Peschke, P.; Waldeck, W.; Ehemann, V.; Kissel, M.; Debus, J. Preferential radiosensitization in p53-mutated human tumour cell lines by pentoxifylline-mediated disruption of the G2/M checkpoint control. Int. J. Radiat. Biol. 2002, 78, 721-732.
82. Rodriguez-Bravo, V.; Guaita-Esteruelas, S.; Salvador, N.; Bachs, O.; Agell, N. Different S/M checkpoint responses of tumor and non tumor cell lines to DNA replication inhibition. Cancer Res. 2007, 67, 11648-11656.
83. Sarkaria, J.N.; Busby, E.C.; Tibbetts, R.S.; Roos, P.; Taya, Y.; Karnitz, L.M.; Abraham, R.T. Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine. Cancer Res. 1999, 59, 4375-4382.
84. Abraham, R.T. The ATM-related kinase, hSMG-1, bridges genome and RNA surveillance pathways. DNA Repair (Amst) 2004, 3, 919-925.
85. Nishida, H.; Tatewaki, N.; Nakajima, Y.; Magara, T.; Ko, K.M.; Hamamori, Y.; Konishi, T. Inhibition of ATR protein kinase activity by schisandrin B in DNA damage response. Nucleic Acids Res. 2009, 37, 5678-5689.
86. Nghiem, P.; Park, P.K.; Kim. Y.; Vaziri, C.; Schreiber, S.L. ATR inhibition selectively sensitizes G1 checkpoint-deficient cells to lethal premature chromatin condensation. Proc. Natl. Acad. Sci. USA 2001, 98, 9092-9097.
87. Wilsker, D.; Bunz, F. Loss of ataxia telangiectasia mutated- and Rad3-related function potentiates the effects of chemotherapeutic drugs on cancer cell survival. Mol. Cancer Ther. 2007, 6, 1406-1413.
88. Plunkett, W.; Huang, P.; Xu, Y.Z.; Heinemann, V.; Grunewald, R.; Gandhi, V. Gemcitabine: metabolism, mechanisms of action, and self-potentiation. Semin. Oncol. 1995, 22 (Suppl. 11), 3-10.
89. Karnitz, L.M.; Flatten, K.S.; Wagner, J.M.; Loegering, D.; Hackbarth, J.S.; Arlander, S.J.H.; Vroman, B.T.; Thomas, M.B.; Baek, Y.-U.; Hopkins, K.M.; Lieberman, H.B.; Chen, J.; Cliby, W.A.; Kaufmann, S.H. Gemcitabine-induced activation of checkpoint signaling pathways that affect tumor cell survival. Mol. Pharmacol. 2005, 68, 1636-1644.
90. Parsels, L.A.; Morgan, M.A.; Tanska, D.M.; Parsels, J.D.; Palmer, B.D.; Booth, R.J.; Denny, W.A.; Canman, C.E.; Kraker, A.J.; Lawrence, T.S.; 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.
91. Matthews, D.J.; Yakes, F.M.; Chen, J. and; Tadano, M. and; Bornheim, L. and; Clary, D.O. and; Tai, A. and; Wagner, J.M. and; Miller, N. and; Kim, Y.D. and; Robertson, S. and; Murray, L. and; Karnitz, L.M Pharmacological abrogation of S-phase checkpoint enhances the anti-tumor activity of gemcitabine in vivo. Cell Cycle 2007, 6, 104-110.
92. Mesa, R.A.; Loegering, D.; Powell, H.L.; Flatten, K.; Arlander, S.J.H.; Dai, N.T.; Heldebrant, M.P.; Vroman, B.T.; Smith, B.D.; Karp, J.E.; Eyck, C.J.T.; Erlichman, C.; Kaufmann, S.H.; Karnitz, L.M. Heat shock protein 90 inhibition sensitizes acute myelogenous leukemia cells to cytarabine. Blood 2005, 106, 318-327.
93. Jardim, M.J.; Wang, Q.; Furumai, R.; Wakeman, T.; Goodman, B.K.; Wang, X.-F. Reduced ATR or Chk1 expression leads to chromosome instability and chemosensitization of mismatch repairdeficient colorectal cancer cells. Mol. Biol. Cell 2009, 20, 3801-3809.
94. Ganzinelli, M.; Carrassa, L.; Crippa, F.; Tavecchio, M.; Broggini, M.; Damia, G. Checkpoint kinase 1 down-regulation by an inducible small interfering RNA expression system sensitized in vivo tumors to treatment with 5-fluorouracil. Clin. Cancer Res. 2008, 14, 5131-5141.
95. Wagner, J.M.; Karnitz, L.M. Cisplatin-induced DNA damage activates replication checkpoint signaling components that differentially affect tumor cell survival. Mol. Pharmacol. 2009, 76, 208-214.
96. Lewis, K.A.; Lilly, K.K.; Reynolds, E.A.; Sullivan, W.P.; Kaufmann, S.H.; Cliby, W.A. Ataxia telangiectasia and rad3-related kinase contributes to cell cycle arrest and survival after cisplatin but not oxaliplatin. Mol. Cancer Ther. 2009, 8, 855-863.
97. Nieborowska-Skorska, M.; Stoklosa, T.; Datta, M.; Czechowska, A. and; Rink, L. and; Slupianek, A. and; Koptyra, M. and; Seferynska, I. and; Krszyna, K. and; Blasiak, J. and; Skorski, T. ATR-Chk1 axis protects BCR/ABL leukemia cells from the lethal effect of DNA double-strand breaks. Cell Cycle 2006, 5, 994-1000.
98. Caporali, S.; Levati, L.; Starace, G.; Ragone, G.; Bonmassar, E.; Alvino, E.; D'Atri, S. AKT is activated in an ataxia-telangiectasia and Rad3-related-dependent manner in response to temozolomide and confers protection against drug-induced cell growth inhibition. Mol. Pharmacol. 2008, 74, 173-183.
99. Caporali, S.; Falcinelli, S.; Starace, G.; Russo, M.T.; Bonmassar, E.; Jiricny, J.; D'Atri, S. DNA damage induced by temozolomide signals to both ATM and ATR: role of the mismatch repair system. Mol. Pharmacol. 2004, 66, 478-491.
100. Cliby, W.A.; Lewis, K.A.; Lilly, K.K.; Kaufmann, S.H. S phase and G2 arrests induced by topoisomerase I poisons are dependent on ATR kinase function. J. Biol. Chem. 2002, 277, 1599-1606.
101. Takai, H.; Tominaga, K.; Motoyama, N.; Minamishima, Y.A.; Nagahama, H.; Tsukiyama, T.;Ikeda, K.; Nakayama, K.; Nakanishi, M.; Nakayama, K. Aberrant cell cycle checkpoint function and early embryonic death in Chk1(-/-) mice. Genes Dev. 2000, 14, 1439-1447.
102. Lara, P.N., Jr.; Mack, P.C.; Synold, T.; Frankel, P.; Longmate, J.; Gumerlock, P.H.; Doroshow, J.H.; Gandara, D.R. The cyclin-dependent kinase inhibitor UCN-01 plus cisplatin in advanced solid tumors: a California cancer consortium phase I pharmacokinetic and molecular correlative trial. Clin. Cancer Res. 2005, 11, 4444-4450.
103. Edelman, M.J.; Bauer, K.S., Jr.; Wu, S.; Smith, R.; Bisacia, S.; Dancey, J. Phase I and pharmacokinetic study of 7-hydroxystaurosporine and carboplatin in advanced solid tumors. Clin. Cancer Res. 2007, 13, 2667-2674.
104. Welch, S.; Hirte, H.W.; Carey, M.S.; Hotte, S.J.; Tsao, M.-S.; Brown, S.; Pond, G.R.; Dancey, J.E.; Oza, A.M. UCN-01 in combination with topotecan in patients with advanced recurrent ovarian cancer: a study of the Princess Margaret Hospital Phase II consortium. Gynecol. Oncol. 2007, 106, 305-310.
105. Jimeno, A.; Rudek, M.A.; Purcell, T.; Laheru, D.A.; Messersmith, W.A.; Dancey, J.; Carducci, M.A.; Baker, S.D.; Hidalgo, M.; Donehower, R.C. Phase I and pharmacokinetic study of UCN- 01 in combination with irinotecan in patients with solid tumors. Cancer Chemother. Pharmacol. 2008, 61, 423-433.
106. Kortmansky, J.; Shah, M.A.; Kaubisch, A.; Weyerbacher, A.; Yi, S.; Tong, W.; Sowers, R.; Gonen, M.; O'Reilly, E.; Kemeny, N.; Ilson, D.I.; Saltz, L.B.; Maki, R.G.; Kelsen, D.P.;Schwartz, G.K. Phase I trial of the cyclin-dependent kinase inhibitor and protein kinase C inhibitor 7-hydroxystaurosporine in combination with Fluorouracil in patients with advanced solid tumors. J. Clin. Oncol. 2005, 23, 1875-1884.
107. Zhang, J.; Yang, P.L.; Gray, N.S. Targeting cancer with small molecule kinase inhibitors. Nat. Rev. Cancer 2009, 9, 28-39.
108. Allen, L.F.; Sebolt-Leopold, J.; Meyer, M.B. CI-1040 (PD184352), a targeted signal transduction inhibitor of MEK (MAPKK). Semin. Oncol. 2003, 30, 105-116.
109. Cohen, M.S.; Zhang, C.; Shokat, K.M.; Taunton, J. Structural bioinformatics-based design of selective, irreversible kinase inhibitors. Science 2005, 308, 1318-1321.
110. Rabindran, S.K.; Discafani, C.M.; Rosfjord, E.C.; Baxter, M.; Floyd, M.B.; Golas, J.; Hallett, W.A.; Johnson, B.D.; Nilakantan, R.; Overbeek, E.; Reich, M.F.; Shen, R.; Shi, X.; Tsou, H.-R.; Wang, Y.-F.; Wissner, A. Antitumor activity of HKI-272, an orally active, irreversible inhibitor of the HER-2 tyrosine kinase. Cancer Res. 2004, 64, 3958-3965.
111. Kobayashi, S.; Ji, H.; Yuza, Y.; Meyerson, M.; Wong, K.-K.; Tenen, D.G.; Halmos, B. An alternative inhibitor overcomes resistance caused by a mutation of the epidermal growth factor receptor. Cancer Res. 2005, 65, 7096-7101.
112. Willmore, E.; de Caux, S.; Sunter, N.J.; Tilby, M.J.; Jackson, G.H.; Austin, C.A.; Durkacz, B.W A novel DNA-dependent protein kinase inhibitor, NU7026, potentiates the cytotoxicity of topoisomerase II poisons used in the treatment of leukemia. Blood 2004, 103, 4659-4665.
113. Hickson, I.; Zhao, Y.; Richardson, C.J.; Green, S.J.; Martin, N.M.B.; Orr, A.I.; Reaper, P.M.; Jackson, S.P.; Curtin, N.J.; Smith, G.C.M. Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM. Cancer Res. 2004, 64, 9152-9159.
114. Liu, P.; Cheng, H.; Roberts, T.M.; Zhao, J.J. Targeting the phosphoinositide 3-kinase pathway in cancer. Nat. Rev. Drug Discov. 2009, 8, 627-644.