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Journal of Neuro-Oncology
Published in: Journal of Neuro-Oncology 3/2012

01-05-2012 | Topic Review

Targeting DNA repair and the cell cycle in glioblastoma

Authors: Brian M. Alexander, Nancy Pinnell, Patrick Y. Wen, Alan D’Andrea

Published in: Journal of Neuro-Oncology | Issue 3/2012

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Abstract

Glioblastoma is a disease with poor outcomes despite standard therapy. Specific targeting of the DNA damage response is a strategy that is becoming increasingly employed in oncology and has intriguing potential for improving outcomes in glioblastoma. DNA damage targeting has implications for improving current therapy as well as the potential to leverage inherent differences in glioblastoma cells to widen the therapeutic window.
Literature
1.
2.
Louis DN, Ohgaki H, Wiestler OD et al (2007) WHO Classification of tumours of the central nervous system. IARC Press, Lyon
3.
Stupp R, Hegi ME, Mason WP et al (2009) Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol 10:459–466PubMedCrossRef
4.
Kennedy RD, D’Andrea AD (2006) DNA repair pathways in clinical practice: lessons from pediatric cancer susceptibility syndromes. J Clin Oncol 24:3799–3808PubMedCrossRef
5.
Lengauer C, Kinzler KW, Vogelstein B (1998) Genetic instabilities in human cancers. Nature 396:643–649PubMedCrossRef
6.
Eisen JA, Hanawalt PC (1999) A phylogenomic study of DNA repair genes, proteins, and processes. Mutat Res 435:171–213PubMed
7.
8.
Weinberg RA (2007) The biology of cancer. Garland Science, New York
9.
10.
Zhou B-BS, Bartek J (2004) Targeting the checkpoint kinases: chemosensitization versus chemoprotection. Nat Rev Cancer 4:216–225PubMedCrossRef
11.
Dai Y, Grant S (2010) New insights into checkpoint kinase 1 in the DNA damage response signaling network. Clin Cancer Res 16:376–383PubMedCrossRef
12.
13.
Gerson SL (2004) MGMT: its role in cancer aetiology and cancer therapeutics. Nat Rev Cancer 4:296–307PubMedCrossRef
14.
Bryant HE, Schultz N, Thomas HD et al (2005) Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434:913–917PubMedCrossRef
15.
Farmer H, McCabe N, Lord CJ et al (2005) Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434:917–921PubMedCrossRef
16.
McCabe N, Turner NC, Lord CJ et al (2006) Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-Ribose) polymerase inhibition. Cancer Res 66:8109–8115PubMedCrossRef
17.
Rouse J, Jackson SP (2002) Interfaces between the detection, signaling, and repair of DNA damage. Science 297:547–551PubMedCrossRef
18.
Kao J, Rosenstein BS, Peters S et al (2005) Cellular response to DNA damage. Ann N Y Acad Sci 1066:243–258PubMedCrossRef
19.
20.
21.
Kinsella TJ (2009) Coordination of DNA mismatch repair and base excision repair processing of chemotherapy and radiation damage for targeting resistant cancers. Clin Cancer Res 15:1853–1859PubMedCrossRef
22.
Comprehensive genomic characterization defines human glioblastoma genes and core pathways (2008). Nature 455:1061–1068
23.
Aebi S, Fink D, Gordon R et al (1997) Resistance to cytotoxic drugs in DNA mismatch repair-deficient cells. Clin Cancer Res 3:1763–1767PubMed
24.
Fink D, Aebi S, Howell SB (1998) The role of DNA mismatch repair in drug resistance. Clin Cancer Res 4:1–6PubMed
25.
Hunter C, Smith R, Cahill DP et al (2006) A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy. Cancer Res 66:3987–3991PubMedCrossRef
26.
Hanawalt PC (2002) Subpathways of nucleotide excision repair and their regulation. Oncogene 21:8949–8956PubMedCrossRef
27.
Friedberg EC (2001) How nucleotide excision repair protects against cancer. Nat Rev Cancer 1:22–33PubMedCrossRef
28.
Khanna KK, Jackson SP (2001) DNA double-strand breaks: signaling, repair and the cancer connection. Nat Genet 27:247–254PubMedCrossRef
29.
Bakkenist CJ, Kastan MB (2003) DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation. Nature 421:499–506PubMedCrossRef
30.
Waga S, Stillman B (1998) The DNA replication fork in eukaryotic cells. Annu Rev Biochem 67:721–751PubMedCrossRef
31.
Ding J, Miao ZH, Meng LH et al (2006) Emerging cancer therapeutic opportunities target DNA-repair systems. Trends Pharmacol Sci 27:338–344PubMedCrossRef
32.
Hegi ME, Diserens AC, Gorlia T et al (2005) MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 352:997–1003PubMedCrossRef
33.
Bristow RG, Hill RP (2008) Hypoxia and metabolism. Hypoxia, DNA repair and genetic instability. Nat Rev Cancer 8:180–192PubMedCrossRef
34.
Sedelnikova OA, Bonner WM (2006) GammaH2AX in cancer cells: a potential biomarker for cancer diagnostics, prediction and recurrence. Cell Cycle 5:2909–2913PubMedCrossRef
35.
Thoms J, Bristow RG (2010) DNA repair targeting and radiotherapy: a focus on the therapeutic ratio. YSRAO 20:217–222
36.
Brown JM, Wilson WR (2004) Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer 4:437–447PubMedCrossRef
37.
Chan N, Koritzinsky M, Zhao H et al (2008) Chronic hypoxia decreases synthesis of homologous recombination proteins to offset chemoresistance and radioresistance. Cancer Res 68:605–614PubMedCrossRef
38.
Bindra RS, Schaffer PJ, Meng A et al (2004) Down-regulation of Rad51 and decreased homologous recombination in hypoxic cancer cells. Mol Cell Biol 24:8504–8518PubMedCrossRef
39.
Hegan DC, Lu Y, Stachelek GC et al (2010) Inhibition of poly(ADP-ribose) polymerase down-regulates BRCA1 and RAD51 in a pathway mediated by E2F4 and p130. Proc Natl Acad Sci USA 107:2201–2206PubMedCrossRef
40.
Chalmers AJ, Lakshman M, Chan N et al (2010) Poly(ADP-ribose) polymerase inhibition as a model for synthetic lethality in developing radiation oncology targets. Semin Radiat Oncol 20:274–281PubMedCrossRef
41.
Karran P, Marinus MG (1982) Mismatch correction at O6-methylguanine residues in E. coli DNA. Nature 296:868–869PubMedCrossRef
42.
Liu L, Markowitz S, Gerson SL (1996) Mismatch repair mutations override alkyltransferase in conferring resistance to temozolomide but not to 1,3-bis(2-chloroethyl)nitrosourea. Cancer Res 56:5375–5379PubMed
43.
Hirose Y, Berger MS, Pieper RO (2001) p53 effects both the duration of G2/M arrest and the fate of temozolomide-treated human glioblastoma cells. Cancer Res 61:1957–1963PubMed
44.
Esteller M, Garcia-Foncillas J, Andion E et al (2000) Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med 343:1350–1354PubMedCrossRef
45.
Marchesi F, Turriziani M, Tortorelli G et al (2007) Triazene compounds: mechanism of action and related DNA repair systems. Pharmacol Res Off J Ita Pharmacol Soc 56:275–287
46.
47.
Liu L, Gerson SL (2006) Targeted modulation of MGMT: clinical implications. Clin Cancer Res 12:328–331PubMedCrossRef
48.
Adhikari S, Choudhury S, Mitra PS et al (2008) Targeting base excision repair for chemosensitization. Anticancer Agents Med Chem 8:351–357PubMed
49.
Tang JB, Svilar D, Trivedi RN et al (2011) N-methylpurine DNA glycosylase and DNA polymerase beta modulate BER inhibitor potentiation of glioma cells to temozolomide. Neuro-oncology 13:471–486PubMedCrossRef
50.
Agnihotri S, Wolf A, Munoz DM et al (2011) A GATA4-regulated tumor suppressor network represses formation of malignant human astrocytomas. J Exp Med 208:689–702PubMedCrossRef
51.
Cheng CL, Johnson SP, Keir ST et al (2005) Poly(ADP-ribose) polymerase-1 inhibition reverses temozolomide resistance in a DNA mismatch repair-deficient malignant glioma xenograft. Mol Cancer Ther 4:1364–1368PubMedCrossRef
52.
Hall EJ, Giaccia AJ (2006) Radiobiology for the radiologist, 6th edn. Lippincott Williams & Wilkins, Philadelphia
53.
Digweed M, Sperling K (2004) Nijmegen breakage syndrome: clinical manifestation of defective response to DNA double-strand breaks. DNA Repair (Amst) 3:1207–1217CrossRef
54.
Savitsky K, Bar-Shira A, Gilad S et al (1995) A single ataxia telangiectasia gene with a product similar to PI-3 kinase. Science 268:1749–1753PubMedCrossRef
55.
Stewart GS, Maser RS, Stankovic T et al (1999) The DNA double-strand break repair gene hMRE11 is mutated in individuals with an ataxia-telangiectasia-like disorder. Cell 99:577–587PubMedCrossRef
56.
Bao S, Wu Q, McLendon RE et al (2006) Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature 444:756–760PubMedCrossRef
57.
Kao GD, Jiang Z, Fernandes AM et al (2007) Inhibition of phosphatidylinositol-3-OH kinase/Akt signaling impairs DNA repair in glioblastoma cells following ionizing radiation. J Biol Chem 282:21206–21212PubMedCrossRef
58.
Mukherjee B, McEllin B, Camacho CV et al (2009) EGFRvIII and DNA double-strand break repair: a molecular mechanism for radioresistance in glioblastoma. Cancer Res 69:4252–4259PubMedCrossRef
59.
Toulany M, Rodemann HP (2010) Membrane receptor signaling and control of DNA repair after exposure to ionizing radiation. Nucl Med (Nuklearmedizin) 49(Suppl 1):S26–S30
60.
Quinn JA, Desjardins A, Weingart J et al (2005) Phase I trial of temozolomide plus O6-benzylguanine for patients with recurrent or progressive malignant glioma. J Clin Oncol 23:7178–7187PubMedCrossRef
61.
Quinn JA, Jiang SX, Reardon DA et al (2009) Phase 1 trial of temozolomide plus irinotecan plus O6-benzylguanine in adults with recurrent malignant glioma. Cancer 115:2964–2970PubMedCrossRef
62.
Quinn JA, Jiang SX, Reardon DA et al (2009) Phase II trial of temozolomide plus O6-benzylguanine in adults with recurrent, temozolomide-resistant malignant glioma. J Clin Oncol 27:1262–1267PubMedCrossRef
63.
Quinn JA, Jiang SX, Reardon DA et al (2009) Phase I trial of temozolomide plus O6-benzylguanine 5-day regimen with recurrent malignant glioma. Neuro-oncology 11:556–561PubMedCrossRef
64.
Ranson M, Middleton MR, Bridgewater J et al (2006) Lomeguatrib, a potent inhibitor of O6-alkylguanine-DNA-alkyltransferase: phase I safety, pharmacodynamic, and pharmacokinetic trial and evaluation in combination with temozolomide in patients with advanced solid tumors. Clin Cancer Res 12:1577–1584PubMedCrossRef
65.
Bobola MS, Blank A, Berger MS et al (2001) Apurinic/apyrimidinic endonuclease activity is elevated in human adult gliomas. Clin Cancer Res 7:3510–3518PubMed
66.
Silber JR, Bobola MS, Blank A et al (2002) The apurinic/apyrimidinic endonuclease activity of Ape1/Ref-1 contributes to human glioma cell resistance to alkylating agents and is elevated by oxidative stress. Clin Cancer Res 8:3008–3018PubMed
67.
Bobola MS, Emond MJ, Blank A et al (2004) Apurinic endonuclease activity in adult gliomas and time to tumor progression after alkylating agent-based chemotherapy and after radiotherapy. Clin Cancer Res 10:7875–7883PubMedCrossRef
68.
Schreiber V, Dantzer F, Ame J-C et al (2006) Poly(ADP-ribose): novel functions for an old molecule. Nat Rev Mol Cell Biol 7:517–528PubMedCrossRef
69.
Johnson N, Li Y-C, Walton ZE et al (2011) Compromised CDK1 activity sensitizes BRCA-proficient cancers to PARP inhibition. Nature Med 17:875–882PubMedCrossRef
70.
Hochegger H, Dejsuphong D, Fukushima T et al (2006) Parp-1 protects homologous recombination from interference by Ku and Ligase IV in vertebrate cells. EMBO J 25:1305–1314PubMedCrossRef
71.
Wang M, Wu W, Wu W et al (2006) PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways. Nucleic Acids Res 34:6170–6182PubMedCrossRef
72.
Boulton S, Kyle S, Durkacz BW (1999) Interactive effects of inhibitors of poly(ADP-ribose) polymerase and DNA-dependent protein kinase on cellular responses to DNA damage. Carcinogenesis 20:199–203PubMedCrossRef
73.
Bowman KJ, White A, Golding BT et al (1998) Potentiation of anti-cancer agent cytotoxicity by the potent poly(ADP-ribose) polymerase inhibitors NU1025 and NU1064. Br J Cancer 78:1269–1277PubMedCrossRef
74.
Brock WA, Milas L, Bergh S et al (2004) Radiosensitization of human and rodent cell lines by INO-1001, a novel inhibitor of poly(ADP-ribose) polymerase. Cancer Lett 205:155–160PubMedCrossRef
75.
Calabrese CR, Almassy R, Barton S et al (2004) Anticancer chemosensitization and radiosensitization by the novel poly(ADP-ribose) polymerase-1 inhibitor AG14361. J Natl Cancer Inst 96:56–67PubMedCrossRef
76.
Fernet M, Ponette V, Deniaud-Alexandre E et al (2000) Poly(ADP-ribose) polymerase, a major determinant of early cell response to ionizing radiation. Int J Radiat Biol 76:1621–1629PubMedCrossRef
77.
Noel G, Godon C, Fernet M et al (2006) Radiosensitization by the poly(ADP-ribose) polymerase inhibitor 4-amino-1,8-naphthalimide is specific of the S phase of the cell cycle and involves arrest of DNA synthesis. Mol Cancer Ther 5:564–574PubMedCrossRef
78.
Veuger SJ, Curtin NJ, Richardson CJ et al (2003) Radiosensitization and DNA repair inhibition by the combined use of novel inhibitors of DNA-dependent protein kinase and poly(ADP-ribose) polymerase-1. Cancer Res 63:6008–6015PubMed
79.
Miknyoczki SJ, Jones-Bolin S, Pritchard S et al (2003) Chemopotentiation of temozolomide, irinotecan, and cisplatin activity by CEP-6800, a poly(ADP-ribose) polymerase inhibitor. Mol Cancer Ther 2:371–382PubMedCrossRef
80.
Ratnam K, Low JA (2007) Current development of clinical inhibitors of poly(ADP-ribose) polymerase in oncology. Clin Cancer Res 13:1383–1388PubMedCrossRef
81.
Yap T (2007) First in human phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of KU-0059436 (Ku), a small molecule inhibitor of poly ADP-ribose polymerase (PARP) in cancer patients (p), including BRCA1/2 mutation carriers. J Clin Oncol ASCO Annual Meeting Proceedings Part I 25
82.
Dungey FA, Löser DA, Chalmers AJ (2008) Replication-dependent radiosensitization of human glioma cells by inhibition of poly(ADP-Ribose) polymerase: mechanisms and therapeutic potential. Int J Radiat Oncol Biol Phys 72:1188–1197PubMedCrossRef
83.
Miknyoczki S, Chang H, Grobelny J et al (2007) The selective poly(ADP-ribose) polymerase-1(2) inhibitor, CEP-8983, increases the sensitivity of chemoresistant tumor cells to temozolomide and irinotecan but does not potentiate myelotoxicity. Mol Cancer Ther 6:2290–2302PubMedCrossRef
84.
Friedman HS, Johnson SP, Dong Q et al (1997) Methylator resistance mediated by mismatch repair deficiency in a glioblastoma multiforme xenograft. Cancer Res 57:2933–2936PubMed
85.
Denny BJ, Wheelhouse RT, Stevens MF et al (1994) NMR and molecular modeling investigation of the mechanism of activation of the antitumor drug temozolomide and its interaction with DNA. Biochemistry 33:9045–9051PubMedCrossRef
86.
Russo AL, Kwon H-C, Burgan WE et al (2009) In vitro and in vivo radiosensitization of glioblastoma cells by the poly (ADP-ribose) polymerase inhibitor E7016. Clin Cancer Res 15:607–612PubMedCrossRef
87.
McEllin B, Camacho CV, Mukherjee B et al (2010) PTEN loss compromises homologous recombination repair in astrocytes: implications for glioblastoma therapy with temozolomide or poly(ADP-ribose) polymerase inhibitors. Cancer Res 70:5457–5464PubMedCrossRef
88.
Mendes-Pereira AM, Martin SA, Brough R et al (2009) Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors. EMBO Mol Med 1:315–322PubMedCrossRef
89.
Nitta M, Kozono D, Kennedy R et al (2010) Targeting EGFR induced oxidative stress by PARP1 inhibition in glioblastoma therapy. PloS ONE 5:e10767PubMedCrossRef
90.
Bai RY, Staedtke V, Riggins GJ (2011) Molecular targeting of glioblastoma: drug discovery and therapies. Trends Mol Med 17:301–312PubMedCrossRef
91.
Shen WH, Balajee AS, Wang J et al (2007) Essential role for nuclear PTEN in maintaining chromosomal integrity. Cell 128:157–170PubMedCrossRef
92.
Matsuoka S, Ballif BA, Smogorzewska A et al (2007) ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage. Science 316:1160–1166PubMedCrossRef
93.
Chakravarti A, Zhai G, Suzuki Y et al (2004) The prognostic significance of phosphatidylinositol 3-kinase pathway activation in human gliomas. J Clin Oncol 22:1926–1933PubMedCrossRef
94.
Network CGAR (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455:1061–1068CrossRef
95.
Parsons DW, Jones S, Zhang X et al (2008) An integrated genomic analysis of human glioblastoma multiforme. Science (New York, NY) 321:1807–1812CrossRef
96.
Ekstrand AJ, Longo N, Hamid ML et al (1994) Functional characterization of an EGF receptor with a truncated extracellular domain expressed in glioblastomas with EGFR gene amplification. Oncogene 9:2313–2320PubMed
97.
Huang HS, Nagane M, Klingbeil CK et al (1997) The enhanced tumorigenic activity of a mutant epidermal growth factor receptor common in human cancers is mediated by threshold levels of constitutive tyrosine phosphorylation and unattenuated signaling. J Biol Chem 272:2927–2935PubMedCrossRef
98.
Nishikawa R, Ji XD, Harmon RC et al (1994) A mutant epidermal growth factor receptor common in human glioma confers enhanced tumorigenicity. Proc Natl Acad Sci USA 91:7727–7731PubMedCrossRef
99.
Golding SE, Morgan RN, Adams BR et al (2009) Pro-survival AKT and ERK signaling from EGFR and mutant EGFRvIII enhances DNA double-strand break repair in human glioma cells. Cancer Biol Ther 8:730–738PubMedCrossRef
100.
Mukherjee B, Choy H, Nirodi C et al (2010) Targeting nonhomologous end-joining through epidermal growth factor receptor inhibition: rationale and strategies for radiosensitization. YSRAO 20:250–257
101.
Brown PD, Krishnan S, Sarkaria JN et al (2008) Phase I/II trial of erlotinib and temozolomide with radiation therapy in the treatment of newly diagnosed glioblastoma multiforme: North Central Cancer Treatment Group Study N0177. J Clin Oncol 26:5603–5609PubMedCrossRef
102.
Peereboom DM, Shepard DR, Ahluwalia MS et al (2010) Phase II trial of erlotinib with temozolomide and radiation in patients with newly diagnosed glioblastoma multiforme. J Neurooncol 98:93–99PubMedCrossRef
103.
Prados MD, Chang SM, Butowski N et al (2009) Phase II study of erlotinib plus temozolomide during and after radiation therapy in patients with newly diagnosed glioblastoma multiforme or gliosarcoma. J Clin Oncol 27:579–584PubMedCrossRef
104.
Chen G, Yuan SS, Liu W et al (1999) Radiation-induced assembly of Rad51 and Rad52 recombination complex requires ATM and c-Abl. J Biol Chem 274:12748–12752PubMedCrossRef
105.
Slupianek A, Hoser G, Majsterek I et al (2002) Fusion tyrosine kinases induce drug resistance by stimulation of homology-dependent recombination repair, prolongation of G(2)/M phase, and protection from apoptosis. Mol Cell Biol 22:4189–4201PubMedCrossRef
106.
Russell JS, Brady K, Burgan WE et al (2003) Gleevec-mediated inhibition of Rad51 expression and enhancement of tumor cell radiosensitivity. Cancer Res 63:7377–7383PubMed
107.
Geng L, Shinohara ET, Kim D et al (2006) STI571 (Gleevec) improves tumor growth delay and survival in irradiated mouse models of glioblastoma. Int J Radiat Oncol Biol Phys 64:263–271PubMedCrossRef
108.
Wen PY, Yung WKA, Lamborn KR et al (2006) Phase I/II study of imatinib mesylate for recurrent malignant gliomas: North American Brain Tumor Consortium Study 99-08. Clin Cancer Res 12:4899–4907PubMedCrossRef
109.
Barker CA, Powell SN (2010) Enhancing radiotherapy through a greater understanding of homologous recombination. YSRAO 20:267–273 e263
110.
Murakawa Y, Sonoda E, Barber LJ et al (2007) Inhibitors of the proteasome suppress homologous DNA recombination in mammalian cells. Cancer Res 67:8536–8543PubMedCrossRef
111.
Shi W, Ma Z, Willers H et al (2008) Disassembly of MDC1 foci is controlled by ubiquitin-proteasome-dependent degradation. J Biol Chem 283:31608–31616PubMedCrossRef
112.
Jacquemont C, Taniguchi T (2007) Proteasome function is required for DNA damage response and fanconi anemia pathway activation. Cancer Res 67:7395–7405PubMedCrossRef
113.
Kubicek GJ, Werner-Wasik M, Machtay M et al (2009) Phase I trial using proteasome inhibitor bortezomib and concurrent temozolomide and radiotherapy for central nervous system malignancies. Int J Radiat Oncol Biol Phys 74:433–439PubMedCrossRef
114.
115.
Lau CC, Pardee AB (1982) Mechanism by which caffeine potentiates lethality of nitrogen mustard. Proc Natl Acad Sci USA 79:2942–2946PubMedCrossRef
116.
Hirai H, Iwasawa Y, Okada M et al (2009) Small-molecule inhibition of Wee1 kinase by MK-1775 selectively sensitizes p53-deficient tumor cells to DNA-damaging agents. Mol Cancer Ther 8:2992–3000PubMedCrossRef
117.
Wang Y, Decker SJ, Sebolt-Leopold J (2004) Knockdown of Chk1, Wee1 and Myt1 by RNA interference abrogates G2 checkpoint and induces apoptosis. Cancer Biol Ther 3:305–313PubMedCrossRef
118.
Mizuarai S, Yamanaka K, Itadani H et al (2009) Discovery of gene expression-based pharmacodynamic biomarker for a p53 context-specific anti-tumor drug Wee1 inhibitor. Mol Cancer 8:34PubMedCrossRef
119.
Wang Y, Li J, Booher RN et al (2001) Radiosensitization of p53 mutant cells by PD0166285, a novel G(2) checkpoint abrogator. Cancer Res 61:8211–8217PubMed
120.
Parker LL, Piwnica-Worms H (1992) Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase. Science 257:1955–1957PubMedCrossRef
121.
Watanabe N, Broome M, Hunter T (1995) Regulation of the human WEE1Hu CDK tyrosine 15-kinase during the cell cycle. EMBO J 14:1878–1891PubMed
122.
123.
Akinaga S, Nomura K, Gomi K et al (1993) Enhancement of antitumor activity of mitomycin C in vitro and in vivo by UCN-01, a selective inhibitor of protein kinase C. Cancer Chemother Pharmacol 32:183–189PubMedCrossRef
124.
Arlander SJ, Eapen AK, Vroman BT et al (2003) Hsp90 inhibition depletes Chk1 and sensitizes tumor cells to replication stress. J Biol Chem 278:52572–52577PubMedCrossRef
125.
Flatten K, Dai NT, Vroman BT et al (2005) The role of checkpoint kinase 1 in sensitivity to topoisomerase I poisons. J Biol Chem 280:14349–14355PubMedCrossRef
126.
Hirose Y, Berger MS, Pieper RO (2001) Abrogation of the Chk1-mediated G(2) checkpoint pathway potentiates temozolomide-induced toxicity in a p53-independent manner in human glioblastoma cells. Cancer Res 61:5843–5849PubMed
127.
Mesa RA, Loegering D, Powell HL et al (2005) Heat shock protein 90 inhibition sensitizes acute myelogenous leukemia cells to cytarabine. Blood 106:318–327PubMedCrossRef
128.
Shi Z, Azuma A, Sampath D et al (2001) S-phase arrest by nucleoside analogues and abrogation of survival without cell cycle progression by 7-hydroxystaurosporine. Cancer Res 61:1065–1072PubMed
129.
Syljuasen RG, Sorensen CS, Nylandsted J et al (2004) Inhibition of Chk1 by CEP-3891 accelerates mitotic nuclear fragmentation in response to ionizing radiation. Cancer Res 64:9035–9040PubMedCrossRef
130.
Teng M, Zhu J, Johnson MD et al (2007) Structure-based design and synthesis of (5-arylamino-2H-pyrazol-3-yl)-biphenyl-2′,4′-diols as novel and potent human CHK1 inhibitors. J Med Chem 50:5253–5256PubMedCrossRef
131.
Tse AN, Rendahl KG, Sheikh T et al (2007) CHIR-124, a novel potent inhibitor of Chk1, potentiates the cytotoxicity of topoisomerase I poisons in vitro and in vivo. Clin Cancer Res 13:591–602PubMedCrossRef
132.
Wang GT, Li G, Mantei RA et al (2005) 1-(5-Chloro-2-alkoxyphenyl)-3-(5-cyanopyrazin-2-yl)ureas [correction of cyanopyrazi] as potent and selective inhibitors of Chk1 kinase: synthesis, preliminary SAR, and biological activities. J Med Chem 48:3118–3121PubMedCrossRef
133.
Wang Q, Fan S, Eastman A et al (1996) UCN-01: a potent abrogator of G2 checkpoint function in cancer cells with disrupted p53. J Natl Cancer Inst 88:956–965PubMedCrossRef
134.
Hotte SJ, Oza A, Winquist EW et al (2006) Phase I trial of UCN-01 in combination with topotecan in patients with advanced solid cancers: a Princess Margaret Hospital Phase II Consortium study. Ann Oncol 17:334–340PubMedCrossRef
135.
Kortmansky J, Shah MA, Kaubisch A et al (2005) 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 23:1875–1884PubMedCrossRef
136.
Lara PN Jr, Mack PC, Synold T et al (2005) 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 11:4444–4450PubMedCrossRef
137.
Sausville EA, Arbuck SG, Messmann R et al (2001) Phase I trial of 72-hour continuous infusion UCN-01 in patients with refractory neoplasms. J Clin Oncol 19:2319–2333PubMed
138.
Sampath D, Cortes J, Estrov Z et al (2006) Pharmacodynamics of cytarabine alone and in combination with 7-hydroxystaurosporine (UCN-01) in AML blasts in vitro and during a clinical trial. Blood 107:2517–2524PubMedCrossRef
139.
Welch S, Hirte HW, Carey MS et al (2007) 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 106:305–310PubMedCrossRef
140.
Jin P, Gu Y, Morgan DO (1996) Role of inhibitory CDC2 phosphorylation in radiation-induced G2 arrest in human cells. J Cell Biol 134:963–970PubMedCrossRef
141.
De Witt Hamer PC, Mir SE, Noske D et al (2011) WEE1 kinase targeting combined with DNA-damaging cancer therapy catalyzes mitotic catastrophe. an official journal of the American Association for Cancer Research, Clinical cancer research
142.
Mir SE, De Witt Hamer PC, Krawczyk PM et al (2010) In silico analysis of kinase expression identifies WEE1 as a gatekeeper against mitotic catastrophe in glioblastoma. Cancer Cell 18:244–257PubMedCrossRef
143.
Fernet M, Mégnin-Chanet F, Hall J et al. (2009) Control of the G2/M checkpoints after exposure to low doses of ionising radiation: Implications for hyper-radiosensitivity. DNA Repair (Amst)
144.
Edwards SL, Brough R, Lord CJ et al (2008) Resistance to therapy caused by intragenic deletion in BRCA2. Nature 451:1111–1115PubMedCrossRef
145.
Sakai W, Swisher EM, Karlan BY et al (2008) Secondary mutations as a mechanism of cisplatin resistance in BRCA2-mutated cancers. Nature 451:1116–1120PubMedCrossRef
Metadata
Title
Targeting DNA repair and the cell cycle in glioblastoma
Authors
Brian M. Alexander
Nancy Pinnell
Patrick Y. Wen
Alan D’Andrea
Publication date
01-05-2012
Publisher
Springer US
Published in
Journal of Neuro-Oncology / Issue 3/2012
Print ISSN: 0167-594X
Electronic ISSN: 1573-7373
DOI
https://doi.org/10.1007/s11060-011-0765-4

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Journal of Neuro-Oncology 3/2012 Go to the issue

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Characterization and outcomes of optic nerve gliomas: a population-based analysis

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Stereotactic radiosurgery for primary and metastatic sarcomas involving the spine

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Independent prognostic value of pre-treatment 18-FDG-PET in high-grade gliomas

Case Report

Initial experience with bendamustine in patients with recurrent primary central nervous system lymphoma: a case report

Erratum

Erratum to: The genotoxic effect of radiofrequency waves on mouse brain

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Unrecognized visual field deficits in children with primary central nervous system brain tumors