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Current Medicinal Chemistry

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Review Article

Breaking the DNA Damage Response via Serine/Threonine Kinase Inhibitors to Improve Cancer Treatment

Author(s): Wioletta Rozpędek*, Dariusz Pytel, Alicja Nowak-Zduńczyk, Dawid Lewko, Radosław Wojtczak, J. Alan Diehl and Ireneusz Majsterek*

Volume 26, Issue 8, 2019

Page: [1425 - 1445] Pages: 21

DOI: 10.2174/0929867325666180117102233

Price: $65

Abstract

Multiple, both endogenous and exogenous, sources may induce DNA damage and DNA replication stress. Cells have developed DNA damage response (DDR) signaling pathways to maintain genomic stability and effectively detect and repair DNA lesions. Serine/ threonine kinases such as Ataxia-telangiectasia mutated (ATM) and Ataxia-telangiectasia and Rad3-Related (ATR) are the major regulators of DDR, since after sensing stalled DNA replication forks, DNA double- or single-strand breaks, may directly phosphorylate and activate their downstream targets, that play a key role in DNA repair, cell cycle arrest and apoptotic cell death. Interestingly, key components of DDR signaling networks may constitute an attractive target for anti-cancer therapy through two distinct potential approaches: as chemoand radiosensitizers to enhance the effectiveness of currently used genotoxic treatment or as single agents to exploit defects in DDR in cancer cells via synthetic lethal approach. Moreover, the newest data reported that serine/threonine protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) is also closely associated with cancer development and progression. Thereby, utilization of small-molecule, serine/threonine kinase inhibitors may provide a novel, groundbreaking, anti-cancer treatment strategy. Currently, a range of potent, highlyselective toward ATM, ATR and PERK inhibitors has been discovered, but after foregoing study, additional investigations are necessary for their future clinical use.

Keywords: Cancer, DNA damage response, ATM, ATR, PERK, kinase inhibitors, cancer treatment.

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[1]
Ma, X.; Yu, H. Global burden of cancer. Yale J. Biol. Med., 2006, 79(3-4), 85-94.
[2]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer Statistics, 2017. CA Cancer J. Clin., 2017, 67(1), 7-30.
[3]
Kanavos, P. The rising burden of cancer in the developing world. Ann Oncol, 2006, 14(Suppl 8), viii15-viii23.
[4]
Jackson, S.P. Detecting, signalling and repairing DNA double-strand breaks. Biochem. Soc. Trans., 2001, 29(Pt 6), 655-661.
[5]
Majsterek, I.; Slupianek, A.; Hoser, G.; Skórski, T.; Blasiak, J. ABL-fusion oncoproteins activate multi-pathway of DNA repair: Role in drug resistance? Biochimie, 2004, 86(1), 53-65.
[6]
Hakem, R. DNA-damage repair; the good, the bad, and the ugly. EMBO J., 2008, 27(4), 589-605.
[7]
Ciccia, A.; Elledge, S.J. The DNA damage response: Making it safe to play with knives. Mol. Cell, 2010, 40(2), 179-204.
[8]
Lindahl, T. Instability and decay of the primary structure of DNA. Nature, 1993, 362(6422), 709-715.
[9]
Yao, Y.; Dai, W. Genomic Instability and Cancer. J. Carcinog. Mutagen., 2014, 5, 1000165.
[10]
De Bont, R.; van Larebeke, N. Endogenous DNA damage in humans: A review of quantitative data. Mutagenesis, 2004, 19(3), 169-185.
[11]
Przybylowska, K.; Kabzinski, J.; Sygut, A.; Dziki, L.; Dziki, A.; Majsterek, I. An association selected polymorphisms of XRCC1, OGG1 and MUTYH gene and the level of efficiency oxidative DNA damage repair with a risk of colorectal cancer. Mutat. Res., 2013, 745-746, 6-15.
[12]
Dietlein, F.; Thelen, L.; Reinhardt, H.C. Cancer-specific defects in DNA repair pathways as targets for personalized therapeutic approaches. Trends Genet., 2014, 30(8), 326-339.
[13]
Jackson, S.P.; Bartek, J. The DNA-damage response in human biology and disease. Nature, 2009, 461(7267), 1071-1078.
[14]
O’Connor, M.J.; Martin, N.M.; Smith, G.C. Targeted cancer therapies based on the inhibition of DNA strand break repair. Oncogene, 2007, 26(56), 7816-7824.
[15]
Kastan, M.B.; Bartek, J. Cell-cycle checkpoints and cancer. Nature, 2004, 432(7015), 316-323.
[16]
Hosoya, N.; Miyagawa, K. Targeting DNA damage response in cancer therapy. Cancer Sci., 2014, 105(4), 370-388.
[17]
Macheret, M.; Halazonetis, T.D. DNA replication stress as a hallmark of cancer. Annu. Rev. Pathol., 2015, 10, 425-448.
[18]
Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell, 2011, 144(5), 646-674.
[19]
Weber, A.M.; Ryan, A.J. ATM and ATR as therapeutic targets in cancer. Pharmacol. Ther., 2015, 149, 124-138.
[20]
Negrini, S.; Gorgoulis, V.G.; Halazonetis, T.D. Genomic instability--an evolving hallmark of cancer. Nat. Rev. Mol. Cell Biol., 2010, 11(3), 220-228.
[21]
Goldstein, M.; Kastan, M.B. The DNA damage response: implications for tumor responses to radiation and chemotherapy. Annu. Rev. Med., 2015, 66, 129-143.
[22]
Liu, L.J.; Wang, W.; Huang, S.Y.; Hong, Y.; Li, G.; Lin, S.; Tian, J.; Cai, Z.; Wang, H.D.; Ma, D.L.; Leung, C.H. Inhibition of the Ras/Raf interaction and repression of renal cancer xenografts in vivo by an enantiomeric iridium(iii) metal-based compound. Chem. Sci. (Camb.), 2017, 8(7), 4756-4763.
[23]
Leung, C.H.; Chan, D.S.; Yang, H.; Abagyan, R.; Lee, S.M.; Zhu, G.Y.; Fong, W.F.; Ma, D.L. A natural product-like inhibitor of NEDD8-activating enzyme. Chem. Commun. (Camb.), 2011, 47(9), 2511-2513.
[24]
Ma, D.L.; Chan, D.S.; Wei, G.; Zhong, H.J.; Yang, H.; Leung, L.T.; Gullen, E.A.; Chiu, P.; Cheng, Y.C.; Leung, C.H. Virtual screening and optimization of Type II inhibitors of JAK2 from a natural product library. Chem. Commun. (Camb.), 2014, 50(90), 13885-13888.
[25]
Munoz, L. Non-kinase targets of protein kinase inhibitors. Nat. Rev. Drug Discov., 2017, 16(6), 424-440.
[26]
Curtin, N.J. Inhibiting the DNA damage response as a therapeutic manoeuvre in cancer. Br. J. Pharmacol., 2013, 169(8), 1745-1765.
[27]
Rundle, S.; Bradbury, A.; Drew, Y.; Curtin, N.J. Targeting the ATR-CHK1 Axis in Cancer Therapy. Cancers (Basel), 2017, 9(5), E41.
[28]
Stokes, M.P.; Rush, J.; Macneill, J.; Ren, J.M.; Sprott, K.; Nardone, J.; Yang, V.; Beausoleil, S.A.; Gygi, S.P.; Livingstone, M.; Zhang, H.; Polakiewicz, R.D.; Comb, M.J. Profiling of UV-induced ATM/ATR signaling pathways. Proc. Natl. Acad. Sci. USA, 2007, 104(50), 19855-19860.
[29]
Lempiäinen, H.; Halazonetis, T.D. Emerging common themes in regulation of PIKKs and PI3Ks. EMBO J., 2009, 28(20), 3067-3073.
[30]
Mordes, D.A.; Glick, G.G.; Zhao, R.; Cortez, D. TopBP1 activates ATR through ATRIP and a PIKK regulatory domain. Genes Dev., 2008, 22(11), 1478-1489.
[31]
Maréchal, A.; Zou, L. DNA damage sensing by the ATM and ATR kinases. Cold Spring Harb. Perspect. Biol., 2013, 5(9), a012716.
[32]
Shiloh, Y. ATM and related protein kinases: Safeguarding genome integrity. Nat. Rev. Cancer, 2003, 3(3), 155-168.
[33]
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(1), 159-169.
[34]
Tibbetts, R.S.; Brumbaugh, K.M.; Williams, J.M.; Sarkaria, J.N.; Cliby, W.A.; Shieh, S.Y.; Taya, Y.; Prives, C.; Abraham, R.T. A role for ATR in the DNA damage-induced phosphorylation of p53. Genes Dev., 1999, 13(2), 152-157.
[35]
Jiang, X.; Sun, Y.; Chen, S.; Roy, K.; Price, B.D. The FATC domains of PIKK proteins are functionally equivalent and participate in the Tip60-dependent activation of DNA-PKcs and ATM. J. Biol. Chem., 2006, 281(23), 15741-15746.
[36]
Wagner, J.M.; Kaufmann, S.H. Prospects for the Use of ATR Inhibitors to Treat Cancer. Pharmaceuticals (Basel), 2010, 3(5), 1311-1334.
[37]
Bosotti, R.; Isacchi, A.; Sonnhammer, E.L. FAT: A novel domain in PIK-related kinases. Trends Biochem. Sci., 2000, 25(5), 225-227.
[38]
Mordes, D.A.; Cortez, D. Activation of ATR and related PIKKs. Cell Cycle, 2008, 7(18), 2809-2812.
[39]
Li, Y.; Zhang, J.; Gao, W.; Zhang, L.; Pan, Y.; Zhang, S.; Wang, Y. Insights on structural characteristics and ligand binding mechanisms of CDK2. Int. J. Mol. Sci., 2015, 16(5), 9314-9340.
[40]
Hardcastle, I.R.; Golding, B.T.; Griffin, R.J. Designing inhibitors of cyclin-dependent kinases. Annu. Rev. Pharmacol. Toxicol., 2002, 42, 325-348.
[41]
Malumbres, M. Cyclin-dependent kinases. Genome Biol., 2014, 15(6), 122.
[42]
Meyerson, M.; Enders, G.H.; Wu, C.L.; Su, L.K.; Gorka, C.; Nelson, C.; Harlow, E.; Tsai, L.H. A family of human cdc2-related protein kinases. EMBO J., 1992, 11(8), 2909-2917.
[43]
Sausville, E.A. Complexities in the development of cyclin-dependent kinase inhibitor drugs. Trends Mol. Med., 2002, 8(4)(Suppl.), S32-S37.
[44]
Johnson, N.; Shapiro, G.I. Cyclin-dependent kinases (cdks) and the DNA damage response: rationale for cdk inhibitor-chemotherapy combinations as an anticancer strategy for solid tumors. Expert Opin. Ther. Targets, 2010, 14(11), 1199-1212.
[45]
Drapkin, R.; Le Roy, G.; Cho, H.; Akoulitchev, S.; Reinberg, D. Human cyclin-dependent kinase-activating kinase exists in three distinct complexes. Proc. Natl. Acad. Sci. USA, 1996, 93(13), 6488-6493.
[46]
Malumbres, M.; Harlow, E.; Hunt, T.; Hunter, T.; Lahti, J.M.; Manning, G.; Morgan, D.O.; Tsai, L.H.; Wolgemuth, D.J. Cyclin-dependent kinases: A family portrait. Nat. Cell Biol., 2009, 11(11), 1275-1276.
[47]
Pines, J. The cell cycle kinases. Semin. Cancer Biol., 1994, 5(4), 305-313.
[48]
Sherr, C.J. Cancer cell cycles. Science, 1996, 274(5293), 1672-1677.
[49]
Hall, M.; Peters, G. Genetic alterations of cyclins, cyclin-dependent kinases, and Cdk inhibitors in human cancer. Adv. Cancer Res., 1996, 68, 67-108.
[50]
Ortega, S.; Malumbres, M.; Barbacid, M. Cyclin D-dependent kinases, INK4 inhibitors and cancer. Biochim. Biophys. Acta, 2002, 1602(1), 73-87.
[51]
Asghar, U.; Witkiewicz, A.K.; Turner, N.C.; Knudsen, E.S. The history and future of targeting cyclin-dependent kinases in cancer therapy. Nat. Rev. Drug Discov., 2015, 14(2), 130-146.
[52]
Whittaker, S.R.; Walton, M.I.; Garrett, M.D.; Workman, P. The Cyclin-dependent kinase inhibitor CYC202 (R-roscovitine) inhibits retinoblastoma protein phosphorylation, causes loss of Cyclin D1, and activates the mitogen-activated protein kinase pathway. Cancer Res., 2004, 64(1), 262-272.
[53]
Shapiro, G.I. Cyclin-dependent kinase pathways as targets for cancer treatment. J. Clin. Oncol., 2006, 24(11), 1770-1783.
[54]
Sánchez-Martínez, C.; Gelbert, L.M.; Lallena, M.J.; de Dios, A. Cyclin dependent kinase (CDK) inhibitors as anticancer drugs. Bioorg. Med. Chem. Lett., 2015, 25(17), 3420-3435.
[55]
Pentimalli, F.; Giordano, A. Promises and drawbacks of targeting cell cycle kinases in cancer. Discov. Med., 2009, 8(43), 177-180.
[56]
de Azevedo, W.F. Opinion Paper: Targeting Multiple Cyclin-Dependent Kinases (CDKs): A New Strategy for Molecular Docking Studies. Curr. Drug Targets, 2016, 17(1), 2.
[57]
Kitagawa, R.; Kastan, M.B. The ATM-dependent DNA damage signaling pathway. Cold Spring Harb. Symp. Quant. Biol., 2005, 70, 99-109.
[58]
Ta, H.Q.; Gioeli, D. The convergence of DNA damage checkpoint pathways and androgen receptor signaling in prostate cancer. Endocr. Relat. Cancer, 2014, 21(5), R395-R407.
[59]
Bakkenist, C.J.; Kastan, M.B. DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature, 2003, 421(6922), 499-506.
[60]
Barlow, C.; Liyanage, M.; Moens, P.B.; Tarsounas, M.; Nagashima, K.; Brown, K.; Rottinghaus, S.; Jackson, S.P.; Tagle, D.; Ried, T.; Wynshaw-Boris, A. Atm deficiency results in severe meiotic disruption as early as leptonema of prophase I. Development, 1998, 125(20), 4007-4017.
[61]
Abraham, R.T. Cell cycle checkpoint signaling through the ATM and ATR kinases. Genes Dev., 2001, 15(17), 2177-2196.
[62]
Lavin, M.F. ATM and the Mre11 complex combine to recognize and signal DNA double-strand breaks. Oncogene, 2007, 26(56), 7749-7758.
[63]
Paull, T.T.; Lee, J.H. The Mre11/Rad50/Nbs1 complex and its role as a DNA double-strand break sensor for ATM. Cell Cycle, 2005, 4(6), 737-740.
[64]
Burma, S.; Chen, B.P.; Murphy, M.; Kurimasa, A.; Chen, D.J. ATM phosphorylates histone H2AX in response to DNA double-strand breaks. J. Biol. Chem., 2001, 276(45), 42462-42467.
[65]
Tanaka, T.; Huang, X.; Jorgensen, E.; Gietl, D.; Traganos, F.; Darzynkiewicz, Z.; Albino, A.P. ATM activation accompanies histone H2AX phosphorylation in A549 cells upon exposure to tobacco smoke. BMC Cell Biol., 2007, 8, 26.
[66]
Sun, Y.; Xu, Y.; Roy, K.; Price, B.D. DNA damage-induced acetylation of lysine 3016 of ATM activates ATM kinase activity. Mol. Cell. Biol., 2007, 27(24), 8502-8509.
[67]
Banin, S.; Moyal, L.; Shieh, S.; Taya, Y.; Anderson, C.W.; Chessa, L.; Smorodinsky, N.I.; Prives, C.; Reiss, Y.; Shiloh, Y.; Ziv, Y. Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science, 1998, 281(5383), 1674-1677.
[68]
Shieh, S.Y.; Ahn, J.; Tamai, K.; Taya, Y.; Prives, C. The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites. Genes Dev., 2000, 14(3), 289-300.
[69]
Brown, E.J.; Baltimore, D. Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance. Genes Dev., 2003, 17(5), 615-628.
[70]
Thu, H.E.; Hussain, Z.; Mohamed, I.N.; Shuid, A.N. Eurycoma longifolia, a potential phytomedicine for the treatment of cancer: Evidence of p53-mediated apoptosis in cancerous cells. Curr. Drug Targets, 2017.
[71]
Shangary, S.; Wang, S. Targeting the MDM2-p53 interaction for cancer therapy. Clin. Cancer Res., 2008, 14(17), 5318-5324.
[72]
Sun, W.; Tang, L. MDM2 Increases Drug Resistance in Cancer Cells by Inducing EMT Independent of p53. Curr. Med. Chem., 2016, 23(40), 4529-4539.
[73]
Liu, D.; Huang, C.L.; Kameyama, K.; Hayashi, E.; Yamauchi, A.; Sumitomo, S.; Yokomise, H. Topoisomerase IIalpha gene expression is regulated by the p53 tumor suppressor gene in nonsmall cell lung carcinoma patients. Cancer, 2002, 94(8), 2239-2247.
[74]
Arcy, D. N.; Gabrielli, B. Topoisomerase II Inhibitors and Poisons, and the Influence of Cell Cycle Checkpoints. Curr. Med. Chem., 2017, 24(15), 1504-1519.
[75]
Alarcon-Vargas, D.; Ronai, Z. p53-Mdm2--the affair that never ends. Carcinogenesis, 2002, 23(4), 541-547.
[76]
Kobet, E.; Zeng, X.; Zhu, Y.; Keller, D.; Lu, H. MDM2 inhibits p300-mediated p53 acetylation and activation by forming a ternary complex with the two proteins. Proc. Natl. Acad. Sci. USA, 2000, 97(23), 12547-12552.
[77]
Lee, Y.; Lim, H.S. Skp2 Inhibitors: Novel Anticancer Strategies. Curr. Med. Chem., 2016, 23(22), 2363-2379.
[78]
Chène, P. Inhibiting the p53-MDM2 interaction: an important target for cancer therapy. Nat. Rev. Cancer, 2003, 3(2), 102-109.
[79]
Gannon, H.S.; Woda, B.A.; Jones, S.N. ATM phosphorylation of Mdm2 Ser394 regulates the amplitude and duration of the DNA damage response in mice. Cancer Cell, 2012, 21(5), 668-679.
[80]
Herbig, U.; Jobling, W.A.; Chen, B.P.; Chen, D.J.; Sedivy, J.M. Telomere shortening triggers senescence of human cells through a pathway involving ATM, p53, and p21(CIP1), but not p16(INK4a). Mol. Cell, 2004, 14(4), 501-513.
[81]
Sullivan, K.D.; Gallant-Behm, C.L.; Henry, R.E.; Fraikin, J.L.; Espinosa, J.M. The p53 circuit board. Biochim. Biophys. Acta, 2012, 1825(2), 229-244.
[82]
Rozpedek, W.; Nowak, A.; Pytel, D.; Diehl, J.A.; Majsterek, I. Molecular basis of human diseases and targeted therapy based on small-molecule inhibitors of ER stress-induced signaling pathways. Curr. Mol. Med., 2017, 17(2), 118-132.
[83]
Matsuoka, S.; Rotman, G.; Ogawa, A.; Shiloh, Y.; Tamai, K.; Elledge, S.J. Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro. Proc. Natl. Acad. Sci. USA, 2000, 97(19), 10389-10394.
[84]
Shen, T.; Huang, S. The role of Cdc25A in the regulation of cell proliferation and apoptosis. Anticancer. Agents Med. Chem., 2012, 12(6), 631-639.
[85]
Falck, J.; Mailand, N.; Syljuåsen, R.G.; Bartek, J.; Lukas, J. The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis. Nature, 2001, 410(6830), 842-847.
[86]
Thanasoula, M.; Escandell, J.M.; Suwaki, N.; Tarsounas, M. ATM/ATR checkpoint activation downregulates CDC25C to prevent mitotic entry with uncapped telomeres. EMBO J., 2012, 31(16), 3398-3410.
[87]
Benada, J.; Macurek, L. Targeting the Checkpoint to Kill Cancer Cells. Biomolecules, 2015, 5(3), 1912-1937.
[88]
Zajac, M.; Muszalska, I.; Jelinska, A. New Molecular Targets of Anticancer Therapy - Current status and perspectives. Curr. Med. Chem., 2016, 23(37), 4176-4220.
[89]
Levin, N.M.; Pintro, V.O.; de Avila, M.B.; de Mattos, B.B.; De Azevedo, W.F. Jr Understanding the Structural Basis for Inhibition of Cyclin-Dependent Kinases. New Pieces in the Molecular Puzzle. Curr. Drug Targets, 2017, 18(9), 1104-1111.
[90]
Heck, G.S.; Pintro, V.O.; Pereira, R.R.; de Ávila, M.B.; Levin, N.M.; de Azevedo, W.F. Supervised machine learning methods applied to predict ligand- binding affinity. Curr. Med. Chem., 2017, 24(23), 2459-2470.
[91]
Luo, Y.; Lou, S.; Deng, X.; Liu, Z.; Li, Y.; Kleiboeker, S.; Qiu, J. Parvovirus B19 infection of human primary erythroid progenitor cells triggers ATR-Chk1 signaling, which promotes B19 virus replication. J. Virol., 2011, 85(16), 8046-8055.
[92]
Ball, H.L.; Myers, J.S.; Cortez, D. ATRIP binding to replication protein A-single-stranded DNA promotes ATR-ATRIP localization but is dispensable for Chk1 phosphorylation. Mol. Biol. Cell, 2005, 16(5), 2372-2381.
[93]
Bomgarden, R.D.; Yean, D.; Yee, M.C.; Cimprich, K.A. A novel protein activity mediates DNA binding of an ATR-ATRIP complex. J. Biol. Chem., 2004, 279(14), 13346-13353.
[94]
Yan, S.; Michael, W.M. TopBP1 and DNA polymerase-alpha directly recruit the 9-1-1 complex to stalled DNA replication forks. J. Cell Biol., 2009, 184(6), 793-804.
[95]
Liu, Q.; Guntuku, S.; Cui, X.S.; 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(12), 1448-1459.
[96]
Jeong, S.Y.; Kumagai, A.; Lee, J.; Dunphy, W.G. Phosphorylated claspin interacts with a phosphate-binding site in the kinase domain of Chk1 during ATR-mediated activation. J. Biol. Chem., 2003, 278(47), 46782-46788.
[97]
Liu, S.; Bekker-Jensen, S.; Mailand, N.; Lukas, C.; Bartek, J.; Lukas, J. Claspin operates downstream of TopBP1 to direct ATR signaling towards Chk1 activation. Mol. Cell. Biol., 2006, 26(16), 6056-6064.
[98]
Manic, G.; Obrist, F.; Sistigu, A.; Vitale, I. Trial Watch: Targeting ATM-CHK2 and ATR-CHK1 pathways for anticancer therapy. Mol. Cell. Oncol., 2015, 2(4), e1012976.
[99]
Sandoval, N.; Platzer, M.; Rosenthal, A.; Dörk, T.; Bendix, R.; Skawran, B.; Stuhrmann, M.; Wegner, R.D.; Sperling, K.; Banin, S.; Shiloh, Y.; Baumer, A.; Bernthaler, U.; Sennefelder, H.; Brohm, M.; Weber, B.H.; Schindler, D. Characterization of ATM gene mutations in 66 ataxia telangiectasia families. Hum. Mol. Genet., 1999, 8(1), 69-79.
[100]
Thompson, D.; Duedal, S.; Kirner, J.; McGuffog, L.; Last, J.; Reiman, A.; Byrd, P.; Taylor, M.; Easton, D.F. Cancer risks and mortality in heterozygous ATM mutation carriers. J. Natl. Cancer Inst., 2005, 97(11), 813-822.
[101]
Wang, C.; Jette, N.; Moussienko, D.; Bebb, D.G.; Lees-Miller, S.P. ATM-Deficient Colorectal Cancer Cells Are Sensitive to the PARP Inhibitor Olaparib. Transl. Oncol., 2017, 10(2), 190-196.
[102]
Dombernowsky, S.L.; Weischer, M.; Allin, K.H.; Bojesen, S.E.; Tybjaerg-Hansen, A.; Nordestgaard, B.G. Risk of cancer by ATM missense mutations in the general population. J. Clin. Oncol., 2008, 26(18), 3057-3062.
[103]
Perlman, S.; Becker-Catania, S.; Gatti, R.A. Ataxia-telangiectasia: diagnosis and treatment. Semin. Pediatr. Neurol., 2003, 10(3), 173-182.
[104]
Choi, M.; Kipps, T.; Kurzrock, R. ATM Mutations in Cancer: Therapeutic Implications. Mol. Cancer Ther., 2016, 15(8), 1781-1791.
[105]
Hammond, E.M.; Muschel, R.J. Radiation and ATM inhibition: The heart of the matter. J. Clin. Invest., 2014, 124(8), 3289-3291.
[106]
Rainey, M.D.; Charlton, M.E.; Stanton, R.V.; Kastan, M.B. Transient inhibition of ATM kinase is sufficient to enhance cellular sensitivity to ionizing radiation. Cancer Res., 2008, 68(18), 7466-7474.
[107]
Velic, D.; Couturier, A.M.; Ferreira, M.T.; Rodrigue, A.; Poirier, G.G.; Fleury, F.; Masson, J.Y. DNA Damage Signalling and Repair Inhibitors: The Long-Sought-After Achilles’ Heel of Cancer. Biomolecules, 2015, 5(4), 3204-3259.
[108]
Blasina, A.; Price, B.D.; Turenne, G.A.; McGowan, C.H. Caffeine inhibits the checkpoint kinase ATM. Curr. Biol., 1999, 9(19), 1135-1138.
[109]
Sarkaria, J.N.; Tibbetts, R.S.; Busby, E.C.; Kennedy, A.P.; Hill, D.E.; Abraham, R.T. Inhibition of phosphoinositide 3-kinase related kinases by the radiosensitizing agent wortmannin. Cancer Res., 1998, 58(19), 4375-4382.
[110]
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(17), 4375-4382.
[111]
Welling, A.; Hofmann, F.; Wegener, J.W. Inhibition of L-type Cav1.2 Ca2+ channels by 2,(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002) and 2-[1-(3-dimethyl-aminopropyl)-5-methoxyindol-3-yl]-3-(1H-indol-3-yl) maleimide (Go6983). Mol. Pharmacol., 2005, 67(2), 541-544.
[112]
Pasapera Limón, A.M.; Herrera-Muñoz, J.; Gutiérrez-Sagal, R.; Ulloa-Aguirre, A. The phosphatidylinositol 3-kinase inhibitor LY294002 binds the estrogen receptor and inhibits 17beta-estradiol-induced transcriptional activity of an estrogen sensitive reporter gene. Mol. Cell. Endocrinol., 2003, 200(1-2), 199-202.
[113]
Vlahos, C.J.; Matter, W.F.; Hui, K.Y.; Brown, R.F. A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J. Biol. Chem., 1994, 269(7), 5241-5248.
[114]
Hickson, I.; Zhao, Y.; Richardson, C.J.; Green, S.J.; Martin, N.M.; Orr, A.I.; Reaper, P.M.; Jackson, S.P.; Curtin, N.J.; Smith, G.C. Identification and characterization of a novel and specific inhibitor of the ataxia-telangiectasia mutated kinase ATM. Cancer Res., 2004, 64(24), 9152-9159.
[115]
Biddlestone-Thorpe, L.; Sajjad, M.; Rosenberg, E.; Beckta, J.M.; Valerie, N.C.; Tokarz, M.; Adams, B.R.; Wagner, A.F.; Khalil, A.; Gilfor, D.; Golding, S.E.; Deb, S.; Temesi, D.G.; Lau, A.; O’Connor, M.J.; Choe, K.S.; Parada, L.F.; Lim, S.K.; Mukhopadhyay, N.D.; Valerie, K. ATM kinase inhibition preferentially sensitizes p53-mutant glioma to ionizing radiation. Clin. Cancer Res., 2013, 19(12), 3189-3200.
[116]
Golding, S.E.; Rosenberg, E.; Valerie, N.; Hussaini, I.; Frigerio, M.; Cockcroft, X.F.; Chong, W.Y.; Hummersone, M.; Rigoreau, L.; Menear, K.A.; O’Connor, M.J.; Povirk, L.F.; van Meter, T.; Valerie, K. Improved ATM kinase inhibitor KU-60019 radiosensitizes glioma cells, compromises insulin, AKT and ERK prosurvival signaling, and inhibits migration and invasion. Mol. Cancer Ther., 2009, 8(10), 2894-2902.
[117]
Batey, M.A.; Zhao, Y.; Kyle, S.; Richardson, C.; Slade, A.; Martin, N.M.; Lau, A.; Newell, D.R.; Curtin, N.J. Preclinical evaluation of a novel ATM inhibitor, KU59403, in vitro and in vivo in p53 functional and dysfunctional models of human cancer. Mol. Cancer Ther., 2013, 12(6), 959-967.
[118]
Grosjean-Raillard, J.; Tailler, M.; Adès, L.; Perfettini, J.L.; Fabre, C.; Braun, T.; De Botton, S.; Fenaux, P.; Kroemer, G. ATM mediates constitutive NF-kappaB activation in high-risk myelodysplastic syndrome and acute myeloid leukemia. Oncogene, 2009, 28(8), 1099-1109.
[119]
Murga, M.; Campaner, S.; Lopez-Contreras, A.J.; Toledo, L.I.; Soria, R.; Montaña, M.F.; Artista, L.; Schleker, T.; Guerra, C.; Garcia, E.; Barbacid, M.; Hidalgo, M.; Amati, B.; Fernandez-Capetillo, O. Exploiting oncogene-induced replicative stress for the selective killing of Myc-driven tumors. Nat. Struct. Mol. Biol., 2011, 18(12), 1331-1335.
[120]
Gilad, O.; Nabet, B.Y.; Ragland, R.L.; Schoppy, D.W.; Smith, K.D.; Durham, A.C.; Brown, E.J. Combining ATR suppression with oncogenic Ras synergistically increases genomic instability, causing synthetic lethality or tumorigenesis in a dosage-dependent manner. Cancer Res., 2010, 70(23), 9693-9702.
[121]
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(3), 478-491.
[122]
Sarkaria, J.N.; Eshleman, J.S. ATM as a target for novel radiosensitizers. Semin. Radiat. Oncol., 2001, 11(4), 316-327.
[123]
Karnitz, L.M.; Zou, L. Molecular Pathways: Targeting ATR in Cancer Therapy. Clin. Cancer Res., 2015, 21(21), 4780-4785.
[124]
Peasland, A.; Wang, L.Z.; Rowling, E.; Kyle, S.; Chen, T.; Hopkins, A.; Cliby, W.A.; Sarkaria, J.; Beale, G.; Edmondson, R.J.; Curtin, N.J. Identification and evaluation of a potent novel ATR inhibitor, NU6027, in breast and ovarian cancer cell lines. Br. J. Cancer, 2011, 105(3), 372-381.
[125]
Toledo, L.I.; Murga, M.; Zur, R.; Soria, R.; Rodriguez, A.; Martinez, S.; Oyarzabal, J.; Pastor, J.; Bischoff, J.R.; Fernandez-Capetillo, O. A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations. Nat. Struct. Mol. Biol., 2011, 18(6), 721-727.
[126]
Wieringa, H.W.; van der Zee, A.G.; de Vries, E.G.; van Vugt, M.A. Breaking the DNA damage response to improve cervical cancer treatment. Cancer Treat. Rev., 2016, 42, 30-40.
[127]
Charrier, J.D.; Durrant, S.J.; Golec, J.M.; Kay, D.P.; Knegtel, R.M.; MacCormick, S.; Mortimore, M.; O’Donnell, M.E.; Pinder, J.L.; Reaper, P.M.; Rutherford, A.P.; Wang, P.S.; Young, S.C.; Pollard, J.R. Discovery of potent and selective inhibitors of ataxia telangiectasia mutated and Rad3 related (ATR) protein kinase as potential anticancer agents. J. Med. Chem., 2011, 54(7), 2320-2330.
[128]
Prevo, R.; Fokas, E.; Reaper, P.M.; Charlton, P.A.; Pollard, J.R.; McKenna, W.G.; Muschel, R.J.; Brunner, T.B. The novel ATR inhibitor VE-821 increases sensitivity of pancreatic cancer cells to radiation and chemotherapy. Cancer Biol. Ther., 2012, 13(11), 1072-1081.
[129]
Reaper, P.M.; Griffiths, M.R.; Long, J.M.; Charrier, J.D.; Maccormick, S.; Charlton, P.A.; Golec, J.M.; Pollard, J.R. Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR. Nat. Chem. Biol., 2011, 7(7), 428-430.
[130]
Pires, I.M.; Olcina, M.M.; Anbalagan, S.; Pollard, J.R.; Reaper, P.M.; Charlton, P.A.; McKenna, W.G.; Hammond, E.M. Targeting radiation-resistant hypoxic tumour cells through ATR inhibition. Br. J. Cancer, 2012, 107(2), 291-299.
[131]
Fujisawa, H.; Nakajima, N.I.; Sunada, S.; Lee, Y.; Hirakawa, H.; Yajima, H.; Fujimori, A.; Uesaka, M.; Okayasu, R. VE-821, an ATR inhibitor, causes radiosensitization in human tumor cells irradiated with high LET radiation. Radiat. Oncol., 2015, 10, 175.
[132]
Fokas, E.; Prevo, R.; Pollard, J.R.; Reaper, P.M.; Charlton, P.A.; Cornelissen, B.; Vallis, K.A.; Hammond, E.M.; Olcina, M.M.; Gillies McKenna, W.; Muschel, R.J.; Brunner, T.B. Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation. Cell Death Dis., 2012, 3, e441.
[133]
Hall, A.B.; Newsome, D.; Wang, Y.; Boucher, D.M.; Eustace, B.; Gu, Y.; Hare, B.; Johnson, M.A.; Milton, S.; Murphy, C.E.; Takemoto, D.; Tolman, C.; Wood, M.; Charlton, P.; Charrier, J.D.; Furey, B.; Golec, J.; Reaper, P.M.; Pollard, J.R. Potentiation of tumor responses to DNA damaging therapy by the selective ATR inhibitor VX-970. Oncotarget, 2014, 5(14), 5674-5685.
[134]
Vendetti, F.P.; Lau, A.; Schamus, S.; Conrads, T.P.; O’Connor, M.J.; Bakkenist, C.J. The orally active and bioavailable ATR kinase inhibitor AZD6738 potentiates the anti-tumor effects of cisplatin to resolve ATM-deficient non-small cell lung cancer in vivo. Oncotarget, 2015, 6(42), 44289-44305.
[135]
Guichard, S.M.; Brown, E.; Odedra, R.; Hughes, A.; Heathcote, D.; Barnes, J.; Lau, A.; Powell, S.; Jones, C.D.; Nissink, W.; Foote, K.M.; Jewsbury, P.J.; Pass, M. The pre-clinical in vitro and in vivo activity of AZD6738: A potent and selective inhibitor of ATR kinase. AACR Canc Res, 2013, 73(8), 3343.
[136]
Dillon, M.T.; Barker, H.E.; Pedersen, M.; Hafsi, H.; Bhide, S.A.; Newbold, K.L.; Nutting, C.M.; McLaughlin, M.; Harrington, K.J. Radiosensitization by the ATR Inhibitor AZD6738 through Generation of Acentric Micronuclei. Mol. Cancer Ther., 2017, 16(1), 25-34.
[137]
Min, A. Im, S.A.; Jang, H.; Kim, S.; Lee, M.; Kim, D.K.; Yang, Y.; Kim, H.J.; Lee, K.H.; Kim, J.W.; Kim, T.Y.; Oh, D.Y.; Brown, J.; Lau, A.; O’Connor, M.J.; Bang, Y.J. AZD6738, a novel oral inhibitor of atr, induces synthetic lethality with ATM deficiency in gastric cancer cells. Mol. Cancer Ther., 2017, 16(4), 566-577.
[138]
Kim, H.J.; Min, A.; Im, S.A.; Jang, H.; Lee, K.H.; Lau, A.; Lee, M.; Kim, S.; Yang, Y.; Kim, J.; Kim, T.Y.; Oh, D.Y.; Brown, J.; O’Connor, M.J.; Bang, Y.J. Anti-tumor activity of the ATR inhibitor AZD6738 in HER2 positive breast cancer cells. Int. J. Cancer, 2017, 140(1), 109-119.
[139]
Hendriks, C.M.; Hartkamp, J.; Wiezorek, S.; Steinkamp, A.D.; Rossetti, G.; Lüscher, B.; Bolm, C. Sulfoximines as ATR inhibitors: Analogs of VE-821. Bioorg. Med. Chem. Lett., 2017, 27(12), 2659-2662.
[140]
Yadav, R.K.; Chae, S.W.; Kim, H.R.; Chae, H.J. Endoplasmic reticulum stress and cancer. J. Cancer Prev., 2014, 19(2), 75-88.
[141]
Bravo, R.; Parra, V.; Gatica, D.; Rodriguez, A.E.; Torrealba, N.; Paredes, F.; Wang, Z.V.; Zorzano, A.; Hill, J.A.; Jaimovich, E.; Quest, A.F.; Lavandero, S. Endoplasmic reticulum and the unfolded protein response: Dynamics and metabolic integration. Int. Rev. Cell Mol. Biol., 2013, 301, 215-290.
[142]
Vandewynckel, Y.P.; Laukens, D.; Geerts, A.; Bogaerts, E.; Paridaens, A.; Verhelst, X.; Janssens, S.; Heindryckx, F.; Van Vlierberghe, H. The paradox of the unfolded protein response in cancer. Anticancer Res., 2013, 33(11), 4683-4694.
[143]
Zhang, K.; Kaufman, R.J. Signaling the unfolded protein response from the endoplasmic reticulum. J. Biol. Chem., 2004, 279(25), 25935-25938.
[144]
Pytel, D.; Seyb, K.; Liu, M.; Ray, S.S.; Concannon, J.; Huang, M.; Cuny, G.D.; Diehl, J.A.; Glicksman, M.A. Enzymatic characterization of ER stress-dependent kinase, PERK, and development of a high-throughput assay for identification of PERK inhibitors. J. Biomol. Screen., 2014, 19(7), 1024-1034.
[145]
Brewer, J.W.; Diehl, J.A. PERK mediates cell-cycle exit during the mammalian unfolded protein response. Proc. Natl. Acad. Sci. USA, 2000, 97(23), 12625-12630.
[146]
Rozpedek, W.; Pytel, D.; Mucha, B.; Leszczynska, H.; Diehl, J.A.; Majsterek, I. The Role of the PERK/eIF2α/ATF4/CHOP Signaling Pathway in Tumor Progression During Endoplasmic Reticulum Stress. Curr. Mol. Med., 2016, 16(6), 533-544.
[147]
Bauer, M.; Goldstein, M.; Heylmann, D.; Kaina, B. Human monocytes undergo excessive apoptosis following temozolomide activating the ATM/ATR pathway while dendritic cells and macrophages are resistant. PLoS One, 2012, 7(6), e39956.
[148]
Li, G.; Mongillo, M.; Chin, K.T.; Harding, H.; Ron, D.; Marks, A.R.; Tabas, I. Role of ERO1-alpha-mediated stimulation of inositol 1,4,5-triphosphate receptor activity in endoplasmic reticulum stress-induced apoptosis. J. Cell Biol., 2009, 186(6), 783-792.
[149]
Tabas, I.; Ron, D. Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat. Cell Biol., 2011, 13(3), 184-190.
[150]
Miller, E.; Markiewicz, Ł.; Saluk, J.; Majsterek, I. Effect of short-term cryostimulation on antioxidative status and its clinical applications in humans. Eur. J. Appl. Physiol., 2012, 112(5), 1645-1652.
[151]
Olas, B.; Wachowicz, B.; Majsterek, I.; Blasiak, J. Resveratrol may reduce oxidative stress induced by platinum compounds in human plasma, blood platelets and lymphocytes. Anticancer Drugs, 2005, 16(6), 659-665.
[152]
Rozpędek, W.; Pytel, D.; Dziki, Ł.; Nowak, A.; Dziki, A.; Diehl, J.A.; Majsterek, I. Inhibition of PERK-dependent pro-adaptive signaling pathway as a promising approach for cancer treatment. Pol. Przegl. Chir., 2017, 89(3), 7-10.
[153]
Liao, Y.; Gu, F.; Mao, X.; Niu, Q.; Wang, H.; Sun, Y.; Song, C.; Qiu, X.; Tan, L.; Ding, C. Regulation of de novo translation of host cells by manipulation of PERK/PKR and GADD34-PP1 activity during Newcastle disease virus infection. J. Gen. Virol., 2016, 97(4), 867-879.
[154]
Axten, J.M.; Romeril, S.P.; Shu, A.; Ralph, J.; Medina, J.R.; Feng, Y.; Li, W.H.; Grant, S.W.; Heerding, D.A.; Minthorn, E.; Mencken, T.; Gaul, N.; Goetz, A.; Stanley, T.; Hassell, A.M.; Gampe, R.T.; Atkins, C.; Kumar, R. Discovery of GSK2656157: An Optimized PERK Inhibitor Selected for Preclinical Development. ACS Med. Chem. Lett., 2013, 4(10), 964-968.
[155]
Atkins, C.; Liu, Q.; Minthorn, E.; Zhang, S.Y.; Figueroa, D.J.; Moss, K.; Stanley, T.B.; Sanders, B.; Goetz, A.; Gaul, N.; Choudhry, A.E.; Alsaid, H.; Jucker, B.M.; Axten, J.M.; Kumar, R. Characterization of a novel PERK kinase inhibitor with antitumor and antiangiogenic activity. Cancer Res., 2013, 73(6), 1993-2002.

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