Login Register Cart 0
Generic placeholder image

Current Pharmacogenomics and Personalized Medicine

Editor-in-Chief

ISSN (Print): 1875-6921
ISSN (Online): 1875-6913

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Current Translational Insights into MGMT Methylation Regulating Temozolomide Sensitivity and Resistance in Glioblastoma Multiforme

Author(s): Ishmeet Gulati, Harsh Patel, Bala Prabhakar and Sujit Nair*

Volume 17, Issue 2, 2020

Page: [76 - 93] Pages: 18

DOI: 10.2174/1875692118666200309130307

Price: $65

Abstract

Background: Temozolomide is used as frontline chemotherapy in the management of glioblastoma multiforme (GBM); however, its clinical utility is limited by the occurrence of significant resistance, majorly caused due to direct DNA repair. O6- methylguanine-DNA-methyltransferase (MGMT), a DNA repair protein, mediates this direct repair pathway and reverses the activity of temozolomide.

Methods: We characterize and underscore the functional relevance and molecular aspects of MGMT in the development of sensitivity/resistance to temozolomide treatment. We review early translational, as well as clinical, evidence for the role of MGMT in mediating temozolomide resistance in vitro in cell lines, in vivo in small animals as well as in GBM patients.

Results: Various approaches have been delineated to mitigate MGMT-induced temozolomide resistance. The most promising means in discovery biology appears to be the co-administration of MGMT inhibitors such as O6 benzyl guanine or lomeguatrib. Surprisingly, the validation of these pharmacologic inhibitors to assess the reversal of chemoresistance by appropriately designed safety and efficacy trials in combination with temozolomide is yet to be demonstrated.

Conclusion: Taken together, given the regulation of temozolomide resistance by MGMT, intermediate and late discovery groups may focus their efforts on pharmacologic inhibition of MGMT, singly or in combination with radiotherapy or immunotherapy, to combat temozolomide resistance in GBM patients. In addition, one may speculate that the combined clinical use of temozolomide with a drug regulator-approved MGMT inhibitor as well as an immune checkpoint inhibitor such as nivolumab may prove beneficial. Future studies may also investigate any inter-ethnic variability in population pharmacogenetics of MGMT and pharmacometric approaches to optimize cancer precision medicine.

Keywords: Glioblastoma, MGMT, temozolomide, methylation, chemotherapy, alkylating agents, resistance, sensitivity.

« Previous
Graphical Abstract

[1]
Holland EC. Glioblastoma multiforme: The terminator. Proc Natl Acad Sci USA 2000; 97(12): 6242-4..
[http://dx.doi.org/10.1073/pnas.97.12.6242] [PMID: 10841526]
[2]
Thakkar JP, Dolecek TA, Horbinski C, Ostrom QT, Lightner DD, Sloan B, et al. Epidemiologic and molecular prognostic review of glioblastoma. Cancer Epidemiol Biomarkers Prev 2014; 23(10): 1985-96.
[http://dx.doi.org/10.1158/1055-9965.EPI-14-0275 ] [PMID: 25053711]
[3]
Brain and Other Nervous System Cancer - Cancer Stat Facts. Brain and Other Nervous System Cancer - Cancer Stat Facts 2018. [online] Available at:. https://seer.cancer. gov/statfacts/html/brain.html
[4]
Ellor SV, Pagano-Young TA, Avgeropoulos NG. Glioblastoma: Background, standard treatment paradigms, and supportive care considerations. J Law Med Ethics 2014; 42(2): 171-82.
[http://dx.doi.org/10.1111/jlme.12133 ] [PMID: 25040381]
[5]
Dasgupta A, Gupta T, Jalali R. Indian data on central nervous tumors: A summary of published work. South Asian J Cancer 2016; 5(3): 147-53.
[http://dx.doi.org/10.4103/2278-330X.187589] [PMID: 27606302]
[6]
Davis ME. Glioblastoma: Overview of disease and treatment. Clin J Oncol Nurs 2016; 20(5)(Suppl.): S2-8..
[http://dx.doi.org/10.1188/16.CJON.S1.2-8] [PMID: 27668386]
[7]
Oppenlander ME, Wolf AB, Snyder LA, Bina R, Wilson JR, Coons SW, et al. An extent of resection threshold for recurrent glioblastoma and its risk for neurological morbidity. J Neurosurg 2014; 120(4): 846-53..
[http://dx.doi.org/10.3171/2013.12.JNS13184] [PMID: 24484232]
[8]
Stupp R, Hegi ME, Mason WP, van den Bent MJ, Taphoorn MJ, Janzer RC, et al. 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 2009; 10(5): 459-66.
[http://dx.doi.org/10.1016/S1470-2045(09)70025-7 ] [PMID: 19269895]
[9]
Wood DE. National Comprehensive Cancer Network (NCCN) clinical practice guidelines for lung cancer screening. Thorac Surg Clin 2015; 25(2): 185-97.
[http://dx.doi.org/10.1016/j.thorsurg.2014.12.003 ] [PMID: 25901562]
[10]
Minniti G, Muni R, Lanzetta G, Marchetti P, Enrici RM. Chemotherapy for glioblastoma: Current treatment and future perspectives for cytotoxic and targeted agents. Anticancer Res 2009; 29(12): 5171-84.
[PMID: 20044633]
[11]
Gerson SL. MGMT: Its role in cancer aetiology and cancer therapeutics. Nat Rev Cancer 2004; 4(4): 296-307.
[http://dx.doi.org/10.1038/nrc1319 ] [PMID: 15057289]
[12]
Jones PA, Baylin SB. The fundamental role of epigenetic events in cancer. Nat Rev Genet 2002; 3(6): 415-28.
[http://dx.doi.org/10.1038/nrg816 ] [PMID: 12042769]
[13]
Soejima H, Zhao W, Mukai T. Epigenetic silencing of the MGMT gene in cancer. Biochem Cell Biol 2005; 83(4): 429-37.
[http://dx.doi.org/10.1139/o05-140 ] [PMID: 16094446]
[14]
Takahashi S, Hall J, Montesano R. Temporal cell-type-specific mRNA expression of O6-methylguanine-DNA methyltransferases in liver of rats treated with dimethylnitrosamine. Am J Pathol 1996; 148(2): 497-507.
[PMID: 8579112]
[15]
Grombacher T, Mitra S, Kaina B. Induction of the alkyltransferase (MGMT) gene by DNA damaging agents and the glucocorticoid dexamethasone and comparison with the response of base excision repair genes. Carcinogenesis 1996; 17(11): 2329-36..
[http://dx.doi.org/10.1093/carcin/17.11.2329] [PMID: 8968045]
[16]
Boldogh I, Ramana CV, Chen Z, Biswas T, Hazra TK, Grosch S, et al. Regulation of expression of the DNA repair gene O6-methylguanine-DNA methyltransferase via protein kinase C-mediated signaling. Cancer Res 1998; 58(17): 3950-6.
[PMID: 9731508]
[17]
Martiny-Baron G, Fabbro D. Classical PKC isoforms in cancer.Pharmacol Res 2007; 55(6): 477-86..
[http://dx.doi.org/10.1016/j.phrs.2007.04.001] [PMID: 17548205]
[18]
Ali AS, Ali S, El-Rayes BF, Philip PA, Sarkar FH. Exploitation of protein kinase C: A useful target for cancer therapy. Cancer Treat Rev 2009; 35(1): 1-8..
[http://dx.doi.org/10.1016/j.ctrv.2008.07.006] [PMID: 18778896]
[19]
do Carmo A, Balça-Silva J, Matias D, Lopes MC. PKC signaling in glioblastoma. Cancer Biol Ther 2013; 14(4): 287-94.
[http://dx.doi.org/10.4161/cbt.23615 ] [PMID: 23358475]
[20]
Wortzel I, Seger R. The ERK Cascade: Distinct functions within various subcellular organelles. Genes Cancer 2011; 2(3): 195-209..
[http://dx.doi.org/10.1177/1947601911407328] [PMID: 21779493]
[21]
Chen B, Liu J, Ho TT, Ding X, Mo YY. ERK-mediated NF-κB activation through ASIC1 in response to acidosis. Oncogenesis 2016; 5(12)e279
[http://dx.doi.org/10.1038/oncsis.2016.81] [PMID: 27941930]
[22]
Lavon I, Fuchs D, Zrihan D, Efroni G, Zelikovitch B, Fellig Y, et al. Novel mechanism whereby nuclear factor kappaB mediates DNA damage repair through regulation of O(6)-methylguanine-DNA-methyltransferase. Cancer Res 2007; 67(18): 8952-9.
[http://dx.doi.org/10.1158/0008-5472.CAN-06-3820 ] [PMID: 17875738]
[23]
Hegi ME, Diserens AC, Godard S, Dietrich PY, Regli L, Ostermann S, et al. Clinical trial substantiates the predictive value of O-6-methylguanine-DNA methyltransferase promoter methylation in glioblastoma patients treated with temozolomide. Clin Cancer Res 2004; 10(6): 1871-4.
[http://dx.doi.org/10.1158/1078-0432.CCR-03-0384 ] [PMID: 15041700]
[24]
Lee SY. Temozolomide resistance in glioblastoma multiforme. Genes Dis 2016; 3(3): 198-210
[http://dx.doi.org/10.1016/j.gendis.2016.04.007] [PMID: 30258889]
[25]
Christmann M, Nagel G, Horn S, Krahn U, Wiewrodt D, Sommer C, et al. MGMT activity, promoter methylation and immunohistochemistry of pretreatment and recurrent malignant gliomas: A comparative study on astrocytoma and glioblastoma. Int J Cancer 2010; 127(9): 2106-18.
[http://dx.doi.org/10.1002/ijc.25229 ] [PMID: 20131314]
[26]
Weller M, Stupp R, Reifenberger G, Brandes AA, van den Bent MJ, Wick W, et al. MGMT promoter methylation in malignant gliomas: ready for personalized medicine?Nat Rev Neurol 2010; 6(1): 39-51.
[http://dx.doi.org/10.1038/nrneurol.2009.197] [PMID: 19997073]
[27]
Sabharwal A, Middleton MR. Exploiting the role of O6- methylguanine-DNA-methyltransferase (MGMT) in cancer therapy. Curr Opin Pharmacol 2006; 6(4): 355-63..
[http://dx.doi.org/10.1016/j.coph.2006.03.011] [PMID: 16777483]
[28]
Kitange GJ, Carlson BL, Schroeder MA, Grogan PT, Lamont JD, Decker PA, et al. Induction of MGMT expression is associated with temozolomide resistance in glioblastoma xenografts.Neuro-oncol 2009; 11(3): 281-91..
[http://dx.doi.org/10.1215/15228517-2008-090] [PMID: 18952979]
[29]
Thon N, Kreth S, Kreth FW. Personalized treatment strategies in glioblastoma: MGMT promoter methylation status. OncoTargets Ther 2013; 6: 1363-72.
[http://dx.doi.org/10.2147/OTT.S50208 ] [PMID: 24109190]
[30]
Felsberg J, Thon N, Eigenbrod S, Hentschel B, Sabel MC, Westphal M, et al. Promoter methylation and expression of MGMT and the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2 in paired primary and recurrent glioblastomas. Int J Cancer 2011; 129(3): 659-70.
[http://dx.doi.org/10.1002/ijc.26083 ] [PMID: 21425258]
[31]
Tonn JC, Thon N, Schnell O, Kreth FW. Personalized surgical therapy. Ann Oncol 2012; 23(Suppl. 10): x28-32.
[http://dx.doi.org/10.1093/annonc/mds363 ] [PMID: 22987977]
[32]
Bady P, Sciuscio D, Diserens AC, Bloch J, van den Bent MJ, Marosi C, et al. MGMT methylation analysis of glioblastoma on the Infinium methylation BeadChip identifiestwo distinct CpG regions associated with gene silencing and outcome, yielding a prediction model for comparisons across datasets, tumor grades, and CIMP-status. Acta Neuropathol 2012; 124(4): 547-60..
[http://dx.doi.org/10.1007/s00401-012-1016-2] [PMID: 22810491]
[33]
Donson AM, Banerjee A, Gamboni-Robertson F, Fleitz JM, Foreman NK. Protein kinase C zeta isoform is critical for proliferation in human glioblastoma cell lines. J Neurooncol 2000; 47(2): 109-15.
[http://dx.doi.org/10.1023/A:1006406208376] [PMID: 10982151]
[34]
Chai RC, Chang YZ, Wang QW, Zhang KN, Li JJ, Hang H, et al. A Novel DNA Methylation-Based Signature Can Predict the Responses of MGMT Promoter Unmethylated Glioblastomas to Temozolomide.Front Genet 2019; 10: 910.
[http://dx.doi.org/10.3389/fgene.2019.00910] [PMID: 31611911]
[35]
Esteller M, Hamilton SR, Burger PC, Baylin SB, Herman JG. Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res 1999; 59(4): 793-7.
[PMID: 10029064]
[36]
Friedman HS, McLendon RE, Kerby T, Dugan M, Bigner SH, Henry AJ, et al. DNA mismatch repair and O6- alkylguanine-DNA alkyltransferase analysis and response to Temodal in newly diagnosed malignant glioma. J Clin Oncol 1998; 16(12): 3851-7.
[http://dx.doi.org/10.1200/JCO.1998.16.12.3851] [PMID: 9850030]
[37]
van Rijn J, Heimans JJ, van den Berg J, van der Valk P, Slotman BJ. Survival of human glioma cells treated with various combination of temozolomide and X-rays. Int J Radiat Oncol Biol Phys 2000; 47(3): 779-84.
[http://dx.doi.org/10.1016/S0360-3016(99)00539-8 ] [PMID: 10837964]
[38]
Damia G, D’Incalci M. Targeting DNA repair as a promising approach in cancer therapy.Eur J Cancer 2007; 43(12): 1791-801.
[http://dx.doi.org/10.1016/j.ejca.2007.05.003] [PMID: 17588740]
[39]
Christmann M, Pick M, Lage H, Schadendorf D, Kaina B. Acquired resistance of melanoma cells to the antineoplastic agent fotemustine is caused by reactivation of the DNA repair gene MGMT. Int J Cancer 2001; 92(1): 123-9.
[http://dx.doi.org/10.1002/1097-0215(200102)9999:9999<::AID-IJC1160>3.0.CO;2-V ] [PMID: 11279615]
[40]
Preuss I, Eberhagen I, Haas S, Eibl HR, Kaufmann M, Von Minckwitz G, et al. O6-methylguanine-DNA methyltransferase activity in breast and brain tumors. Int J Cancer 1995; 61(3): 321-6.
[http://dx.doi.org/10.1002/ijc.2910610308 ] [PMID: 7729942]
[41]
Milsom MD, Woolford LB, Margison GP, Humphries RK, Fairbairn LJ. Enhanced in vivo selection of bone marrow cells by retroviral-mediated coexpression of mutant O6-methylguanine-DNA-methyltransferase and HOXB4. Mol Ther 2004; 10(5): 862-73.
[http://dx.doi.org/10.1016/j.ymthe.2004.07.019] [PMID: 15509504]
[42]
Woolford LB, Southgate TD, Margison GP, Milsom MD, Fairbairn LJ. The P140K mutant of human O(6)-methylguanine-DNA-methyltransferase (MGMT) confers resistance in vitro and in vivo to temozolomide in combination with the novel MGMT inactivator O(6)-(4-bromothenyl)guanine. J Gene Med 2006; 8(1): 29-34.
[http://dx.doi.org/10.1002/jgm.816 ] [PMID: 16075413]
[43]
Xu-Welliver M, Kanugula S, Pegg AE. Isolation of human O6-alkylguanine-DNA alkyltransferase mutants highly resistant to inactivation by O6-benzylguanine. Cancer Res 1998; 58(9): 1936-45.
[PMID: 9581836]
[44]
Chen TC, Chan N, Minea RO, Hartman H, Hofman FM, Schonthal AH. Rare stochastic expression of O6-Methylguanine- DNA Methyltransferase (MGMT) in MGMT-negative melanoma cells determines immediate emergence of drug-resistant populations upon treatment with temozolomide in vitro and in vivo. Cancers (Basel) 2018; 10(10): 362.
[http://dx.doi.org/10.3390/cancers10100362]
[45]
Luke JJ, Schwartz GK. Chemotherapy in the management of advanced cutaneous malignant melanoma. Clin Dermatol 2013; 31(3): 290-7.
[http://dx.doi.org/10.1016/j.clindermatol.2012.08.016 ] [PMID: 23608448]
[46]
Chen TC, Cho HY, Wang W, Barath M, Sharma N, Hofman FM, et al. A novel temozolomide-perillyl alcohol conjugate exhibits superior activity against breast cancer cells in vitro and intracranial triple-negative tumor growth in vivo. Mol Cancer Ther 2014; 13(5): 1181-93.
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0882 ] [PMID: 24623736]
[47]
Perazzoli G, Prados J, Ortiz R, Caba O, Cabeza L, Berdasco M, et al. Temozolomide resistance in glioblastoma cell lines: Implication of MGMT, MMR, P-Glycoprotein and CD133 expression. PLoS One 2015; 10(10)e0140131
[http://dx.doi.org/10.1371/journal.pone.0140131] [PMID: 26447477]
[48]
Gaspar N, Marshall L, Perryman L, Bax DA, Little SE, Viana-Pereira M, et al. MGMT-independent temozolomide resistance in pediatric glioblastoma cells associated with a PI3-kinase-mediated HOX/stem cell gene signature. Cancer Res 2010; 70(22): 9243-52.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-1250 ] [PMID: 20935218]
[49]
Guo J, Cui Q, Jiang W, Liu C, Li D, Zeng Y. Research on DNA methylation of human osteosarcoma cell MGMT and its relationship with cell resistance to alkylating agents. Biochem Cell Biol 2013; 91(4): 209-13.
[http://dx.doi.org/10.1139/bcb-2012-0100 ] [PMID: 23859014]
[50]
Happold C, Roth P, Wick W, Schmidt N, Florea AM, Silginer M, et al. Distinct molecular mechanisms of acquired resistance to temozolomide in glioblastoma cells. J Neurochem 2012; 122(2): 444-55.
[http://dx.doi.org/10.1111/j.1471-4159.2012.07781.x ] [PMID: 22564186]
[51]
Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005; 352(10): 997-1003.
[http://dx.doi.org/10.1056/NEJMoa043331 ] [PMID: 15758010]
[52]
Batchelor TT, Mulholland P, Neyns B, Nabors LB, Campone M, Mason AW, et al. Phase III randomized trial comparing the efficacy of cediranib as monotherapy, and in combination with lomustine, versus lomustine alone in patients with recurrent glioblastoma. J Clin Oncol 2013; 31(26): 3212-8.
[http://dx.doi.org/10.1200/JCO.2012.47.2464] [PMID: 23940216]
[53]
Stritzelberger J, Distel L, Buslei R, Fietkau R, Putz F. Acquired temozolomide resistance in human glioblastoma cell line U251 is caused by mismatch repair deficiency and can be overcome by lomustine 2018. 20(4): 508-16..
[http://dx.doi.org/10.1007/s12094-017-1743-x]
[54]
van Nifterik KA, van den Berg J, van der Meide WF, Ameziane N, Wedekind LE, Steenbergen RDM, et al. Absence of the MGMT protein as well as methylation of the MGMT promoter predict the sensitivity for temozolomide. Br J Cancer 2010; 103(1): 29-35.
[http://dx.doi.org/10.1038/sj.bjc.6605712 ] [PMID: 20517307]
[55]
Chen X, Zhang M, Gan H, Wan H, Lee JH, Fang D, et al. A novel enhancer regulates MGMT expression and promotes temozolomide resistance in glioblastoma. Nat Commun 2018 2018; 9(1): 2949.
[http://dx.doi.org/10.1038/s41467-018-05373-4] [PMID: 30054476]
[56]
Kitange GJ, Mladek AC, Carlson BL, Schroeder MA, Pokorny JL, Cen L, et al. Inhibition of histone deacetylation potentiates the evolution of acquired temozolomide resistance linked to MGMT upregulation in glioblastoma xenografts. Clin Cancer Res 2012; 18(15): 4070-9.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-0560 ] [PMID: 22675172]
[57]
Shlyueva D, Stampfel G, Stark A. Transcriptional enhancers: from properties to genome-wide predictions. Nat Rev Genet 2014; 15(4): 272-86.
[http://dx.doi.org/10.1038/nrg3682 ] [PMID: 24614317]
[58]
Heinz S, Romanoski CE, Benner C, Glass CK. The selection and function of cell type-specific enhancers. Nat Rev Mol Cell Biol 2015; 16(3): 144-54.
[http://dx.doi.org/10.1038/nrm3949 ] [PMID: 25650801]
[59]
Thotakura M, Tirumalasetti N, Krishna R. Role of Ki-67 labeling index as an adjunct to the histopathological diagnosis and grading of astrocytomas. J Cancer Res Ther 2014; 10(3): 641-5.
[PMID: 25313753]
[60]
Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res 2011; 21(3): 381-95.
[http://dx.doi.org/10.1038/cr.2011.22 ] [PMID: 21321607]
[61]
Middleton MR, Kelly J, Thatcher N, Donnelly DJ, McElhinney SR, McMurry TBH, et al. O(6)-(4-bromothenyl)guanine improves the therapeutic index of temozolomide against A375M melanoma xenografts. Int J Cancer 2000; 85(2): 248-52.
[http://dx.doi.org/10.1002/(SICI)1097-0215(20000115)85:2%3C248::AID-IJC16%3E3.0.CO;2-V ] [PMID: 10629085]
[62]
Watson AJ, Sabharwal A, Thorncroft M, McGown G, Kerr R, Bojanic S, et al. Tumor O(6)-methylguanine-DNA methyltransferase inactivation by oral lomeguatrib. Clin Cancer Res 2010; 16(2): 743-9.
[http://dx.doi.org/10.1158/1078-0432.CCR-09-1389 ] [PMID: 20068091]
[63]
Yue W, Brodie A. MCF-7 human breast carcinomas in nude mice as a model for evaluating aromatase inhibitors. J Steroid Biochem Mol Biol 1993; 44(4-6): 671-3.
[http://dx.doi.org/10.1016/0960-0760(93)90278-5 ] [PMID: 8476781]
[64]
Turriziani M, Caporaso P, Bonmassar L, Buccisano F, Amadori S, Venditti A, et al. O6-(4-bromothenyl)guanine (PaTrin-2), a novel inhibitor of O6-alkylguanine DNA alkyl-transferase, increases the inhibitory activity of temozolomide against human acute leukaemia cells in vitro. Pharmacol Res 2006; 53(4): 317-23.
[http://dx.doi.org/10.1016/j.phrs.2005.12.001] [PMID: 16412662]
[65]
Horton TM, Jenkins G, Pati D, Zhang L, Dolan ME, Ribes-Zamora A, et al. Poly(ADP-ribose) polymerase inhibitor ABT-888 potentiates the cytotoxic activity of temozolomide in leukemia cells: Influence of mismatch repair status and O6-methylguanine-DNA methyltransferase activity. Mol Cancer Ther 2009; 8(8): 2232-42.
[http://dx.doi.org/10.1158/1535-7163.MCT-09-0142 ] [PMID: 19671751]
[66]
Sakumi K, Shiraishi A, Shimizu S, Tsuzuki T, Ishikawa T, Sekiguchi M. Methylnitrosourea-induced tumorigenesis in MGMT gene knockout mice. Cancer Res 1997; 57(12): 2415-8.
[PMID: 9192819]
[67]
Shiraishi A, Sakumi K, Sekiguchi M. Increased susceptibility to chemotherapeutic alkylating agents of mice deficient in DNA repair methyltransferase. Carcinogenesis 2000; 21(10): 1879-83.
[http://dx.doi.org/10.1093/carcin/21.10.1879] [PMID: 11023546]
[68]
Fan CH, Liu WL, Cao H, Wen C, Chen L, Jiang G. O6-methylguanine DNA methyltransferase as a promising target for the treatment of temozolomide-resistant gliomas.Cell Death Dis 2013; 4e876
[http://dx.doi.org/10.1038/cddis.2013.388 ] [PMID: 24157870]
[69]
Rasimas JJ, Dalessio PA, Ropson IJ, Pegg AE, Fried MG. Active-site alkylation destabilizes human O6-alkylguanine DNA alkyltransferase. Protein Sci 2004; 13(1): 301-5.
[http://dx.doi.org/10.1110/ps.03319404 ] [PMID: 14691244]
[70]
Li X, Yuan L, Zhao J, Yang H, Yang Y, Zhang Y, et al. Adenovirus-based strategies enhance antitumor capability through p53-mediated downregulation of MGMT in uveal melanoma. Cancer Biol Ther 2017; 18(3): 194-9.
[http://dx.doi.org/10.1080/15384047.2017.1294287 ] [PMID: 28278076]
[71]
Buder K, Gesierich A, Gelbrich G, Goebeler M. Systemic treatment of metastatic uveal melanoma: Review of literature and future perspectives. Cancer Med 2013; 2(5): 674-86.
[http://dx.doi.org/10.1002/cam4.133 ] [PMID: 24403233]
[72]
Zhang H, Wang H, Zhang J, Qian J, Niu B, Fan X, et al. Enhanced therapeutic efficacy by simultaneously targeting two genetic defects in tumors. Mol Ther 2009; 17(1): 57-64.
[http://dx.doi.org/10.1038/mt.2008.236 ] [PMID: 19018252]
[73]
Cun B, Song X, Jia R, Zhao X, Wang H, Ge S, et al. Combination of oncolytic adenovirus and dacarbazine attenuates antitumor ability against uveal melanoma cells via cell cycle block. Cancer Biol Ther 2012; 13(2): 77-84.
[http://dx.doi.org/10.4161/cbt.13.2.18436 ] [PMID: 22336909]
[74]
Ottolino-Perry K, Diallo JS, Lichty BD, Bell JC, McCart JA. Intelligent design: Combination therapy with oncolytic viruses. Mol Ther 2010; 18(2): 251-63.
[http://dx.doi.org/10.1038/mt.2009.283 ] [PMID: 20029399]
[75]
Jiang G, Wei ZP, Pei DS, Xin Y, Liu YQ, Zheng JN. A novel approach to overcome temozolomide resistance in glioma and melanoma: Inactivation of MGMT by gene therapy. Biochem Biophys Res Commun 2011; 406(3): 311-4..
[http://dx.doi.org/10.1016/j.bbrc.2011.02.042] [PMID: 21329652]
[76]
Huang X, Wang L, Zhang H, Wang H, Zhao X, Qian G, et al. Therapeutic efficacy by targeting correction of Notch1-induced aberrants in uveal tumors. PLoS One 2012; 7(8)e44301
[http://dx.doi.org/10.1371/journal.pone.0044301] [PMID: 22937170]
[77]
Wang J, Jia R, Zhang Y, Xu X, Song X, Zhao Y, et al. The role of Bax and Bcl-2 in gemcitabine-mediated cytotoxicity in uveal melanoma cells.Tumour Biol 2014; 35(2): 1169- 75.
[http://dx.doi.org/10.1007/s13277-013-1156-6] [PMID: 24014050]
[78]
Natsume A, Ishii D, Wakabayashi T, Tsuno T, Hatano H, Mizuno M, et al. IFN-beta down-regulates the expression of DNA repair gene MGMT and sensitizes resistant glioma cells to temozolomide. Cancer Res 2005; 65(17): 7573-9.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-0036 ] [PMID: 16140920]
[79]
Ma S, Egyházi S, Ueno T, Lindholm C, Kreklau EL, Stierner U, et al. O6-methylguanine-DNA-methyltrans-ferase expression and gene polymorphisms in relation to chemotherapeutic response in metastatic melanoma. Br J Cancer 2003; 89(8): 1517-23.
[http://dx.doi.org/10.1038/sj.bjc.6601270 ] [PMID: 14562026]
[80]
Wang K, Chen D, Qian Z, Cui D, Gao L, Lou M. Hedgehog/Gli1 signaling pathway regulates MGMT expression and chemoresistance to temozolomide in human glioblastoma. Cancer Cell Int 2017; 17: 117.
[http://dx.doi.org/10.1186/s12935-017-0491-x] [PMID: 29225516]
[81]
Yoon JW, Gilbertson R, Iannaccone S, Iannaccone P, Walterhouse D. Defining a role for Sonic hedgehog pathway activation in desmoplastic medulloblastoma by identifying GLI1 target genes. Int J Cancer 2009; 124(1): 109-19.
[http://dx.doi.org/10.1002/ijc.23929 ] [PMID: 18924150]
[82]
Chen JK, Taipale J, Cooper MK, Beachy PA. Inhibition of Hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes Dev 2002; 16(21): 2743-8.
[http://dx.doi.org/10.1101/gad.1025302 ] [PMID: 12414725]
[83]
Shi Z, Lou M, Zhao Y, Zhang Q, Cui D, Wang K. Effect of all-trans retinoic acid on the differentiation of U87 glioma stem/progenitor cells. Cell Mol Neurobiol 2013; 33(7): 943- 51.
[http://dx.doi.org/10.1007/s10571-013-9960-5] [PMID: 23852377]
[84]
Ulasov IV, Nandi S, Dey M, Sonabend AM, Lesniak MS. Inhibition of Sonic hedgehog and Notch pathways enhances sensitivity of CD133(+) glioma stem cells to temozolomide therapy. Mol Med 2011; 17(1-2): 103-12..
[http://dx.doi.org/10.2119/molmed.2010.00062] [PMID: 20957337]
[85]
Jonasch E, Haluska FG. Interferon in oncological practice: Review of interferon biology, clinical applications, and toxicities. Oncologist 2001; 6(1): 34-55.
[http://dx.doi.org/10.1634/theoncologist.6-1-34] [PMID: 11161227]
[86]
Groves MD, Puduvalli VK, Gilbert MR, Levin VA, Conrad CA, Liu VH, et al. Two phase II trials of temozolomide with interferon-alpha2b (pegylated and non-pegylated) in patients with recurrent glioblastoma multiforme. Br J Cancer 2009; 101(4): 615-20.
[http://dx.doi.org/10.1038/sj.bjc.6605189 ] [PMID: 19672263]
[87]
Qiu ZK, Shen D, Chen YS, Yang QY, Guo CC, Feng BH, et al. Enhanced MGMT expression contributes to temozolomide resistance in glioma stem-like cells. Chin J Cancer 2014; 33(2): 115-22.
[http://dx.doi.org/10.5732/cjc.012.10236 ] [PMID: 23958055]
[88]
Warren K, Bent R, Wolters PL, Prager A, Hanson R, Packer R, et al. A phase 2 study of pegylated interferon α-2b (PEG-Intron(®)) in children with diffuse intrinsic pontine glioma. Cancer 2012; 118(14): 3607-13.
[http://dx.doi.org/10.1002/cncr.26659 ] [PMID: 22086404]
[89]
Shen D, Guo CC, Wang J, Qiu ZK, Sai K, Yang QY, et al. Interferon-α/β enhances temozolomide activity against MGMT-positive glioma stem-like cells. Oncol Rep 2015; 34(5): 2715-21.
[http://dx.doi.org/10.3892/or.2015.4232 ] [PMID: 26329778]
[90]
Binabaj MM, Bahrami A. ShahidSales S, Joodi M, Mashhad MJ, Hassanian SM, et al. The prognostic value of MGMT promoter methylation in glioblastoma: A metaanalysis of clinical trials 2018; 233(1): 378-86.
[http://dx.doi.org/10.1002/jcp.25896]
[91]
Wick W, Platten M, Weller M. New (alternative) temozolomide regimens for the treatment of glioma. Neurooncol 2009; 11(1): 69-79..
[http://dx.doi.org/10.1215/15228517-2008-078] [PMID: 18772354]
[92]
Brock CS, Newlands ES, Wedge SR, Bower M, Evans H, Colquhoun I, et al. Phase I trial of temozolomide using an extended continuous oral schedule. Cancer Res 1998; 58(19): 4363-7.
[PMID: 9766665]
[93]
Bower M, Newlands ES, Bleehen NM, Brada M, Begent RJH, Calvert H, et al. Multicentre CRC phase II trial of temozolomide in recurrent or progressive high-grade glioma. Cancer Chemother Pharmacol 1997; 40(6): 484-8.
[http://dx.doi.org/10.1007/s002800050691 ] [PMID: 9332462]
[94]
Tolcher AW, Gerson SL, Denis L, Geyer C, Hammond LA, Patnaik A, et al. Marked inactivation of O6-alkylguanine-DNA alkyltransferase activity with protracted temozolomide schedules. Br J Cancer 2003; 88(7): 1004-11.
[http://dx.doi.org/10.1038/sj.bjc.6600827 ] [PMID: 12671695]
[95]
Madhusudan S, Hickson ID. DNA repair inhibition: A selective tumour targeting strategy. Trends Mol Med 2005; 11(11): 503-11..
[http://dx.doi.org/10.1016/j.molmed.2005.09.004] [PMID: 16214418]
[96]
Jaeckle KA, Eyre HJ, Townsend JJ, Schulman S, Knudson HM, Yarosh MBB, et al. Correlation of tumor O6 methylguanine-DNA methyltransferase levels with survival of malignant astrocytoma patients treated with bischloroethylnitrosourea: A southwest oncology group study. J Clin Oncol 1998; 16(10): 3310-5..
[http://dx.doi.org/10.1200/JCO.1998.16.10.3310] [PMID: 9779706]
[97]
Anderson P, Aguilera D, Pearson M, Woo S. Outpatient chemotherapy plus radiotherapy in sarcomas: Improving cancer control with radiosensitizing agents. Cancer Contr 2008; 15(1): 38-46..
[http://dx.doi.org/10.1177/107327480801500105] [PMID: 18094659]
[98]
Gilbert MR, Wang M, Aldape KD, Stupp R, Hegi ME, Kurt A, et al. Dose-dense temozolomide for newly diagnosed glioblastoma: A randomized phase III clinical trial. J Clin Oncol 2013; 31(32): 4085-91.
[http://dx.doi.org/10.1200/JCO.2013.49.6968] [PMID: 24101040]
[99]
Pegg AE. Repair of O(6)-alkylguanine by alkyltransferases. Mutat Res 2000; 462(2-3): 83-100.
[http://dx.doi.org/10.1016/S1383-5742(00)00017-X ] [PMID: 10767620]
[100]
Palmisano WA, Divine KK, Saccomanno G, Gilliland FD, Baylin SB, Herman JG, et al. Predicting lung cancer by detecting aberrant promoter methylation in sputum. Cancer Res 2000; 60(21): 5954-8.
[PMID: 11085511]
[101]
Donson AM, Addo-Yobo SO, Handler MH, Gore L, Foreman NK. MGMT promoter methylation correlates with survival benefit and sensitivity to temozolomide in pediatric glioblastoma. Pediatr Blood Cancer 2007; 48(4): 403-7.
[http://dx.doi.org/10.1002/pbc.20803 ] [PMID: 16609952]
[102]
Heynckes S, Daka K, Franco P, Gaebelein A, Frenking JH, Doria-Medina R, et al. Crosslink between Temozolomide and PD-L1 immune-checkpoint inhibition in glioblastoma multiforme. BMC Cancer 2019; 19(1): 117.
[http://dx.doi.org/10.1186/s12885-019-5308-y] [PMID: 30709339]
[103]
Pavelka Z, Zitterbart K, Noskova H, Bajciova V, Slaby O, Sterba J. Effective Immunotherapy of glioblastoma in an adolescent with constitutional mismatch repair-deficiency syndrome. Klin Onkol 2019; 32(1): 70-4.
[http://dx.doi.org/10.14735/amko201970 ] [PMID: 30764633]
[104]
Nair S. Pharmacometrics and systems pharmacology of immune checkpoint inhibitor nivolumab in cancer translational medicine. Adv Mod Oncol Res 2016; 2(1): 18-31.
[http://dx.doi.org/10.18282/amor.v2.i1.46]
[105]
Nair S. LLerena A. New perspectives in personalised medicine for ethnicity in cancer: population pharmacogenomics and pharmacometrics. Drug Metab Pers Ther 2018; 33(2): 61-4..
[http://dx.doi.org/10.1515/dmpt-2018-0008] [PMID: 29688886]
[106]
Nair S, Kong AT. Emerging roles for clinical pharmacometrics in cancer precision medicine.Curr Pharmacol Rep 2018; 4(3): 276-83
[http://dx.doi.org/10.1007/s40495-018-0139-0] [PMID: 30345221]
[107]
Zhang J, Xiao X, Zhu J, Gao Z, Lai X, Zhu X, et al. Lactoferrin- and RGD-comodified, temozolomide and vincristine-coloaded nanostructured lipid carriers for gliomatosis cerebri combination therapy. Int J Nanomedicine 2018; 13: 3039-51.
[http://dx.doi.org/10.2147/IJN.S161163 ] [PMID: 29861635]
[108]
Zhang P, Tang M, Huang Q, Zhao G, Huang N, Zhang X, et al. Combination of 3-methyladenine therapy and Asn-GlyArg (NGR)-modified mesoporous silica nanoparticles loaded with temozolomide for glioma therapy in vitro. Biochem Biophys Res Commun 2019; 509(2): 549-56..
[http://dx.doi.org/10.1016/j.bbrc.2018.12.158] [PMID: 30600180]
[109]
Danhier F, Messaoudi K, Lemaire L, Benoit JP, Lagarce F. Combined anti-Galectin-1 and anti-EGFR siRNA-loaded chitosan-lipid nanocapsules decrease temozolomide resistance in glioblastoma: In vivo evaluation. Int J Pharm 2015; 481(1-2): 154-61..
[http://dx.doi.org/10.1016/j.ijpharm.2015.01.051] [PMID: 25644286]
[110]
Bertucci A, Prasetyanto EA, Septiadi D, Manicardi A, Brognara E, Gambari R, et al. Combined delivery of temozolomide and Anti-miR221 PNA using mesoporous silica nanoparticles induces apoptosis in resistant glioma cells. Small 2015; 11(42): 5687-95.
[http://dx.doi.org/10.1002/smll.201500540 ] [PMID: 26395266]
[111]
Dilnawaz F, Sahoo SK. Enhanced accumulation of curcumin and temozolomide loaded magnetic nanoparticles executes profound cytotoxic effect in glioblastoma spheroid model Eur J Pharm Biopharm 2013; 85(3 Pt A): 452-62
[http://dx.doi.org/10.1016/j.ejpb.2013.07.013] [PMID: 23891772]
[112]
Di Martino A, Pavelkova A, Maciulyte S, Budriene S, Sedlarik V. Polysaccharide-based nanocomplexes for coencapsulation and controlled release of 5-Fluorouracil and Temozolomide. Eur J Pharm Sci 2016; 92:: 276-86.
[http://dx.doi.org/10.1016/j.ejps.2016.05.001] [PMID: 27154260]
[113]
Peng Y, Huang J, Xiao H, Wu T, Shuai X. Codelivery of temozolomide and siRNA with polymeric nanocarrier for effective glioma treatment. Int J Nanomedicine 2018; 13: 3467-80.
[http://dx.doi.org/10.2147/IJN.S164611 ] [PMID: 29942129 ]

Rights & Permissions Print Cite
Article Metrics
16
© 2024 Bentham Science Publishers | Privacy Policy