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靶向胶质母细胞瘤中的复制应激
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Abstract:
胶质母细胞瘤是成人常见的原发性脑肿瘤，病程短，预后差，具有极强的治疗抗性，目前临床治疗仍然以手术切除辅以放化疗为主。近期，新兴的电场疗法被加入到胶质母细胞瘤的辅助疗法中，其是否有效尚存在争议。在过去50年里，胶质母细胞瘤的药物研发停滞不前，临床急需有效的药物改善患者预后。早期研究表明，由于DDR通路的异常上调，GBM (Glioblastoma)是一种先天耐受放化疗的肿瘤。基于现有治疗GBM的方法均会造成DNA损伤的特点，抑制DDR通路激活，加剧复制应激可能是改善GBM患者预后的有效策略。因此，我们对目前GBM的治疗概况以及靶向GBM中的DDR通路，增强现有DNA损伤疗法的相关研究进展进行了综述。
Glioblastoma is a common primary brain tumor among adults with a short course of disease, poor prognosis and elevated treatment resistance. Currently, clinical treatment of GBM is still based on surgical resection supplemented by radiotherapy and chemotherapy. Recently, the emerging tumor-treating fields (TTFs) therapy has been approved to treat GBM as adjuvant therapy, and its effectiveness is still controversial. In the past 50 years, drug development for glioblastoma has stagnated, and there is an urgent need for new drug to improve the outcomes of GBM patient. Early studies have shown that GBM is innately resistant to chemotherapy and radiotherapy due to abnormal upregulation of the DDR pathway. Therefore, based on the characteristics of existing therapies which cause DNA damage to inhibit tumor growth, we reviewed the current treatment of GBM and the related research progress of targeting the DDR pathway in GBM to enhance existing DNA damage therapies.
| [1] | Morgan, L.L. (2015) The Epidemiology of Glioma in Adults: A “State of the Science” Review. Neuro-Oncology, 17, 623-624. https://doi.org/10.1093/neuonc/nou358 |
| [2] | Ostrom, Q.T., Gittleman, H., Liao, P., et al. (2014) CBTRUS Statistical Report: Primary Brain and Central Nervous System Tumors Diagnosed in the United States in 2007-2011. Neuro-Oncology, 16, iv1-iv63.
https://doi.org/10.1093/neuonc/nou223 |
| [3] | Jiang, T., Nam, D.H., Ram, Z., et al. (2021) Clinical Practice Guidelines for the Management of Adult Diffuse Gliomas. Cancer Letters, 499, 60-72. https://doi.org/10.1016/j.canlet.2020.10.050 |
| [4] | Osswald, M., Jung, E., Sahm, F., et al. (2015) Brain Tumour Cells Interconnect to a Functional and Resistant Network. Nature, 528, 93-98. https://doi.org/10.1038/nature16071 |
| [5] | Stupp, R., Hegi, M.E., Mason, W.P., 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. The Lancet Oncology, 10, 459-466. https://doi.org/10.1016/S1470-2045(09)70025-7 |
| [6] | Brandes, A.A., Tosoni, A., Franceschi, E., Reni, M., Gatta, G. and Vecht, C. (2008) Glioblastoma in Adults. Critical Reviews in Oncology/Hematology, 67, 139-152. https://doi.org/10.1016/j.critrevonc.2008.02.005 |
| [7] | Sandmann, T., Bourgon, R., Garcia, J., et al. (2015) Patients with Proneural Glioblastoma May Derive Overall Survival Benefit from the Addition of Bevacizumab to First-Line Radiotherapy and Temozolomide: Retrospective Analysis of the AVAglio Trial. Journal of Clinical Oncology, 33, 2735-2744. https://doi.org/10.1200/JCO.2015.61.5005 |
| [8] | Pasqualetti, F., Gonnelli, A., Molinari, A., et al. (2018) Different Timing to Use Bevacizumab in Patients with Recurrent Glioblastoma: Early versus Delayed Administration. Anticancer Research, 38, 5877-5881.
https://doi.org/10.21873/anticanres.12930 |
| [9] | Chinot, O.L., Wick, W., Mason, W., et al. (2014) Bevacizumab plus Radiotherapy-Temozolomide for Newly Diagnosed Glioblastoma. The New England Journal of Medicine, 370, 709-722. https://doi.org/10.1056/NEJMoa1308345 |
| [10] | Chaudhry, A., Benson, L., Varshaver, M., et al. (2015) NovoTTF？-100A System (Tumor Treating Fields) Transducer Array Layout Planning for Glioblastoma: A NovoTAL？ System User Study. World Journal of Surgical Oncology, 13, Article No. 316. https://doi.org/10.1186/s12957-015-0722-3 |
| [11] | Stupp, R., Taillibert, S., Kanner, A., et al. (2017) Effect of Tumor-Treating Fields Plus Maintenance Temozolomide vs Maintenance Temozolomide Alone on Survival in Patients With Glioblastoma: A Randomized Clinical Trial. Journal of the American Medical Association, 318, 2306-2316. https://doi.org/10.1001/jama.2017.18718 |
| [12] | Rominiyi, O., Vanderlinden, A., Clenton, S.J., Bridgewater, C., Al-Tamimi, Y. and Collis, S.J. (2021) Tumour Treating Fields Therapy for Glioblastoma: Current Advances and Future Directions. British Journal of Cancer, 124, 697-709. https://doi.org/10.1038/s41416-020-01136-5 |
| [13] | Murciano-Goroff, Y.R., Warner, A.B. and Wolchok, J.D. (2020) The Future of Cancer Immunotherapy: Microenvironment-Targeting Combinations. Cell Research, 30, 507-519. https://doi.org/10.1038/s41422-020-0337-2 |
| [14] | Gerstner, E.R. and Fine, R.L. (2007) Increased Permeability of the Blood-Brain Barrier to Chemotherapy in Metastatic Brain Tumors: Establishing a Treatment Paradigm. Journal of Clinical Oncology, 25, 2306-2312.
https://doi.org/10.1200/JCO.2006.10.0677 |
| [15] | Bagchi, S., Chhibber, T., Lahooti, B., Verma, A., Borse, V. and Jayant, R.D. (2019) In-Vitro Blood-Brain Barrier Models for Drug Screening and Permeation Studies: An Overview. Drug Design, Development and Therapy, 13, 3591-3605.
https://doi.org/10.2147/DDDT.S218708 |
| [16] | Chowdhury, E.A., Noorani, B., Alqahtani, F., et al. Understanding the Brain Uptake and Permeability of Small Molecules through the BBB: A Technical Overview. Journal of Cerebral Blood Flow & Metabolism, 41, 1797-1820.
https://doi.org/10.1177/0271678X20985946 |
| [17] | Verhaak, R.G., Hoadley, K.A., Purdom, E., et al. (2010) Integrated Genomic Analysis Identifies Clinically Relevant Subtypes of Glioblastoma Characterized by Abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell, 17, 98-110. https://doi.org/10.1016/j.ccr.2009.12.020 |
| [18] | Neftel, C., Laffy, J., Filbin, M.G., et al. (2019) An Integrative Model of Cellular States, Plasticity, and Genetics for Glioblastoma. Cell, 178, 835-849.E21. https://doi.org/10.1016/j.cell.2019.06.024 |
| [19] | Helleday, T., Petermann, E., Lundin, C., Hodgson, B. and Sharma, R.A. (2008) DNA Repair Pathways as Targets for Cancer Therapy. Nature Reviews Cancer, 8, 193-204. https://doi.org/10.1038/nrc2342 |
| [20] | Huang, Z., Cheng, L., Guryanova, O.A., Wu, Q. and Bao, S. (2010) Cancer Stem Cells in Glioblastoma-Molecular Signaling and Therapeutic Targeting. Protein & Cell, 1, 638-655. https://doi.org/10.1007/s13238-010-0078-y |
| [21] | Morgan, M.A. and Canman, C.E. (2018) Replication Stress: An Achilles’ Heel of Glioma Cancer Stem-Like Cells. Cancer Research, 78, 6713-6716. https://doi.org/10.1158/0008-5472.CAN-18-2439 |
| [22] | Aldape, K., Brindle, K.M., Chesler, L., et al. (2019) Challenges to Curing Primary Brain Tumours. Nature Reviews Clinical Oncology, 16, 509-520. https://doi.org/10.1038/s41571-019-0177-5 |
| [23] | Ngoi, N.Y.L., Pham, M.M., Tan, D.S.P. and Yap, T.A. (2021) Targeting the Replication Stress Response through Synthetic Lethal Strategies in Cancer Medicine. Trends in Cancer, 7, 930-957. https://doi.org/10.1016/j.trecan.2021.06.002 |
| [24] | Zeman, M.K. and Cimprich, K.A. (2014) Causes and Consequences of Replication Stress. Nature Cell Biology, 16, 2-9. https://doi.org/10.1038/ncb2897 |
| [25] | Harper, J.W. and Elledge, S.J. (2007) The DNA Damage Response: Ten Years after. Molecular Cell, 28, 739-745.
https://doi.org/10.1016/j.molcel.2007.11.015 |
| [26] | Blackford, A.N. and Jackson, S.P. (2017) ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response. Molecular Cell, 66, 801-817. https://doi.org/10.1016/j.molcel.2017.05.015 |
| [27] | Jackson, S.P. and Bartek, J. (2009) The DNA-Damage Response in Human Biology and Disease. Nature, 461, 1071- 1078. https://doi.org/10.1038/nature08467 |
| [28] | Toledo, L., Neelsen, K.J. and Lukas, J. (2017) Replication Catastrophe: When a Checkpoint Fails Because of Exhaustion. Molecular Cell, 66, 735-749. https://doi.org/10.1016/j.molcel.2017.05.001 |
| [29] | Damia, G. (2020) Targeting DNA-PK in Cancer. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 821, Article ID: 111692. https://doi.org/10.1016/j.mrfmmm.2020.111692 |
| [30] | Stagni, V., Oropallo, V., Fianco, G., Antonelli, M., Cinà, I. and Barilà, D. (2014) Tug of War between Survival and Death: Exploring ATM Function in Cancer. International Journal of Molecular Sciences, 15, 5388-5409.
https://doi.org/10.3390/ijms15045388 |
| [31] | Armstrong, S.A., Schultz, C.W., Azimi-Sadjadi, A., Brody, J.R. and Pishvaian, M.J. (2019) ATM Dysfunction in Pancreatic Adenocarcinoma and Associated Therapeutic Implications. Molecular Cancer Therapeutics, 18, 1899-1908.
https://doi.org/10.1158/1535-7163.MCT-19-0208 |
| [32] | Curtin, N.J. (2012) DNA Repair Dysregulation from Cancer Driver to Therapeutic Target. Nature Reviews Cancer, 12, 801-817. https://doi.org/10.1038/nrc3399 |
| [33] | Maréchal, A. and Zou, L. (2013) DNA Damage Sensing by the ATM and ATR Kinases. Cold Spring Harbor Perspectives in Biology, 5, a012716. https://doi.org/10.1101/cshperspect.a012716 |
| [34] | Shiloh, Y. and Ziv, Y. (2013) The ATM Protein Kinase: Regulating the Cellular Response to Genotoxic Stress, and More. Nature Reviews Molecular Cell Biology, 14, 197-210. https://doi.org/10.1038/nrm3546 |
| [35] | Ferri, A., Stagni, V. and Barilà, D. (2020) Targeting the DNA Damage Response to Overcome Cancer Drug Resistance in Glioblastoma. International Journal of Molecular Sciences, 21, Article No. 4910.
https://doi.org/10.3390/ijms21144910 |
| [36] | Bakr, A., Oing, C., K？cher, S., et al. (2015) Involvement of ATM in Homologous Recombination after End Resection and RAD51 Nucleofilament Formation. Nucleic Acids Research, 43, 3154-3166. https://doi.org/10.1093/nar/gkv160 |
| [37] | Ciccia, A. and Elledge, S.J. (2010) The DNA Damage Response: Making It Safe to Play with Knives. Molecular Cell, 40, 179-204. https://doi.org/10.1016/j.molcel.2010.09.019 |
| [38] | Mailand, N., Falck, J., Lukas, C., et al. (2000) Rapid Destruction of Human Cdc25A in Response to DNA Damage. Science, 288, 1425-1429. https://doi.org/10.1126/science.288.5470.1425 |
| [39] | Toledo, L.I., Altmeyer, M., Rask, M.B., et al. (2013) ATR Prohibits Replication Catastrophe by Preventing Global Exhaustion of RPA. Cell, 155, 1088-1103. https://doi.org/10.1016/j.cell.2013.10.043 |
| [40] | Damia, G. (2020) Targeting DNA-PK in Cancer. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 821, Article ID: 111692. https://doi.org/10.1016/j.mrfmmm.2020.111692 |
| [41] | Zhang, Y.W., Jones, T.L., Martin, S.E., Caplen, N.J. and Pommier, Y. (2009) Implication of Checkpoint Kinase- Dependent Up-Regulation of Ribonucleotide Reductase R2 in DNA Damage Response. Journal of Biological Chemistry, 284, 18085-18095. https://doi.org/10.1074/jbc.M109.003020 |
| [42] | Li, X. and Heyer, W.D. (2008) Homologous Recombination in DNA Repair and DNA Damage Tolerance. Cell Research, 18, 99-113. https://doi.org/10.1038/cr.2008.1 |
| [43] | Chang, H.H.Y., Pannunzio, N.R., Adachi, N. and Lieber, M.R. (2017) Non-Homologous DNA End Joining and Alternative Pathways to Double-Strand Break Repair. Nature Reviews Molecular Cell Biology, 18, 495-506.
https://doi.org/10.1038/nrm.2017.48 |
| [44] | Degan, P., Cappelli, E., Regis, S. and Ravera, S. (2019) New Insights and Perspectives in Fanconi Anemia Research. Trends in Molecular Medicine, 25, 167-170. https://doi.org/10.1016/j.molmed.2019.01.003 |
| [45] | Denny, B.J., Wheelhouse, R.T., Stevens, M.F., Tsang, L.L. and Slack, J.A. (1994) NMR and Molecular Modeling Investigation of the Mechanism of Activation of the Antitumor Drug Temozolomide and Its Interaction with DNA. Biochemistry, 33, 9045-9051. https://doi.org/10.1021/bi00197a003 |
| [46] | Tisdale, M.J. (1987) Antitumor Imidazotetrazines—XV. Role of Guanine O6 Alkylation in the Mechanism of Cytotoxicity of Imidazotetrazinones. Biochemical Pharmacology, 36, 457-462.
https://doi.org/10.1016/0006-2952(87)90351-0 |
| [47] | Mojas, N., Lopes, M. and Jiricny, J. (2007) Mismatch Repair-Dependent Processing of Methylation Damage Gives Rise to Persistent Single-Stranded Gaps in Newly Replicated DNA. Genes & Development, 21, 3342-3355.
https://doi.org/10.1101/gad.455407 |
| [48] | Eich, M., Roos, W.P., Nikolova, T. and Kaina, B. (2013) Contribution of ATM and ATR to the Resistance of Glioblastoma and Malignant Melanoma Cells to the Methylating Anticancer Drug Temozolomide. Molecular Cancer Therapeutics, 12, 2529-2540. https://doi.org/10.1158/1535-7163.MCT-13-0136 |
| [49] | Matt, S. and Hofmann, T.G. (2016) The DNA Damage-Induced Cell Death Response: A Roadmap to Kill Cancer Cells. Cellular and Molecular Life Sciences, 73, 2829-2850. https://doi.org/10.1007/s00018-016-2130-4 |
| [50] | Fròsina, G., Profumo, A., Marubbi, D., Marcello, D., Ravetti, J.L. and Daga, A. (2018) ATR Kinase Inhibitors NVP- BEZ235 and AZD6738 Effectively Penetrate the Brain after Systemic Administration. Radiation Oncology, 13, Article No. 76. https://doi.org/10.1186/s13014-018-1020-3 |
| [51] | Carruthers, R.D., Ahmed, S.U., Ramachandran, S., et al. (2018) Replication Stress Drives Constitutive Activation of the DNA Damage Response and Radioresistance in Glioblastoma Stem-Like Cells. Cancer Research, 78, 5060-5071.
https://doi.org/10.1158/0008-5472.CAN-18-0569 |
| [52] | Biddlestone-Thorpe, L., Sajjad, M., Rosenberg, E., et al. (2013) ATM Kinase Inhibition Preferentially Sensitizes p53- Mutant Glioma to Ionizing Radiation. Clinical Cancer Research, 19, 3189-3200.
https://doi.org/10.1158/1078-0432.CCR-12-3408 |
| [53] | Durant, S.T., Zheng, L., Wang, Y., et al. (2018) The Brain-Penetrant Clinical ATM Inhibitor AZD1390 Radiosensitizes and Improves Survival of Preclinical Brain Tumor Models. Science Advances, 4, eaat1719.
https://doi.org/10.1126/sciadv.aat1719 |
| [54] | Jucaite, A., Stenkrona, P., Cselényi, Z., et al. (2021) Brain Exposure of the ATM Inhibitor AZD1390 in Humans—A Positron Emission Tomography Study. Neuro-Oncology, 23, 687-696. https://doi.org/10.1093/neuonc/noaa238 |
| [55] | Bao, S., Wu, Q., McLendon, R.E., et al. (2006) Glioma Stem Cells Promote Radioresistance by Preferential Activation of the DNA Damage Response. Nature, 444, 756-760. https://doi.org/10.1038/nature05236 |
| [56] | Patties, I., Kallendrusch, S., B？hme, L., et al. (2019) The Chk1 Inhibitor SAR-020106 Sensitizes Human Glioblastoma Cells to Irradiation, to Temozolomide, and to Decitabine Treatment. Journal of Experimental & Clinical Cancer Research, 38, Article No. 420. https://doi.org/10.1186/s13046-019-1434-2 |
| [57] | Alexander, B., Supko, J., Agar, N., Ahluwalia, M., Desai, A., Dietrich, J., Kaley, T., Peereboom, D., Takebe, N., Desideri, S., et al. (2018) ACTR-14. Phase I Study of AZD1775 with Radiation Therapy (RT) and Temozolomide (TMZ) in Patients with Newly Diagnosed Glioblastoma (GBM) and Evaluation of Intratumoral Drug Distribution in Patients with Recurrent GBM. Neuro-Oncology, 20, vi13-vi14. https://doi.org/10.1093/neuonc/noy148.048 |
| [58] | Wick, W., Weller, M., van den Bent, M., et al. (2014) MGMT Testing—The Challenges for Biomarker-Based Glioma Treatment. Nature Reviews Neurology, 10, 372-385. https://doi.org/10.1038/nrneurol.2014.100 |
| [59] | Wood, R.D., Mitchell, M., Sgouros, J. and Lindahl, T. (2001) Human DNA Repair Genes. Science, 291, 1284-1289.
https://doi.org/10.1126/science.1056154 |
| [60] | Hegi, M.E., Diserens, A.C., Gorlia, T., et al. (2005) MGMT Gene Silencing and Benefit from Temozolomide in Glioblastoma. The New England Journal of Medicine, 352, 997-1003. https://doi.org/10.1056/NEJMoa043331 |
| [61] | Mellai, M., Monzeglio, O., Piazzi, A., et al. (2012) MGMT Promoter Hypermethylation and Its Associations with Genetic Alterations in a Series of 350 Brain Tumors. Journal of Neuro-Oncology, 107, 617-631.
https://doi.org/10.1007/s11060-011-0787-y |
| [62] | Fan, C.H., Liu, W.L., Cao, H., Wen, C., Chen, L. and Jiang, G. (2013) O6-Methylguanine DNA Methyltransferase as a Promising Target for the Treatment of Temozolomide-Resistant Gliomas. Cell Death & Disease, 4, e876.
https://doi.org/10.1038/cddis.2013.388 |
| [63] | Jackson, C.B., Noorbakhsh, S.I., Sundaram, R.K., et al. (2019) Temozolomide Sensitizes MGMT-Deficient Tumor Cells to ATR Inhibitors. Cancer Research, 79, 4331-4338. https://doi.org/10.1158/0008-5472.CAN-18-3394 |
| [64] | Middleton, M.R. and Margison, G.P. (2003) Improvement of Chemotherapy Efficacy by Inactivation of a DNA-Repair Pathway. The Lancet Oncology, 4, 37-44. https://doi.org/10.1016/S1470-2045(03)00959-8 |
| [65] | Quinn, J.A., Jiang, S.X., Reardon, D.A., et al. (2009) Phase II Trial of Temozolomide plus O6-Benzylguanine in Adults with Recurrent, Temozolomide-Resistant Malignant Glioma. Journal of Clinical Oncology, 27, 1262-1267.
https://doi.org/10.1200/JCO.2008.18.8417 |
| [66] | Hickson, I.D. (1997) Base Excision Repair of DNA Damage. Landes Bioscience and Chapman & Hall, Austin. |
| [67] | Wu, S., Li, X., Gao, F., de Groot, J.F., Koul, D. and Yung, W.K.A. (2021) PARP-Mediated PARylation of MGMT Is Critical to Promote Repair of Temozolomide-Induced O6-Methylguanine DNA Damage in Glioblastoma. Neuro-Oncology, 23, 920-931. https://doi.org/10.1093/neuonc/noab003 |
| [68] | Higuchi, F., Nagashima, H., Ning, J., Koerner, M.V.A., Wakimoto, H. and Cahill, D.P. (2020) Restoration of Temozolomide Sensitivity by PARP Inhibitors in Mismatch Repair Deficient Glioblastoma Is Independent of Base Excision Repair. Clinical Cancer Research, 26, 1690-1699. https://doi.org/10.1158/1078-0432.CCR-19-2000 |
| [69] | Farmer, H., McCabe, N., Lord, C.J., et al. (2005) Targeting the DNA Repair Defect in BRCA Mutant Cells as a Therapeutic Strategy. Nature, 434, 917-921. https://doi.org/10.1038/nature03445 |
| [70] | Bryant, H.E., Schultz, N., Thomas, H.D., et al. (2005) Specific Killing of BRCA2-Deficient Tumours with Inhibitors of Poly(ADP-Ribose) Polymerase. Nature, 434, 913-917. https://doi.org/10.1038/nature03443 |
| [71] | Mateo, J., Lord, C.J., Serra, V., et al. (2019) A Decade of Clinical Development of PARP Inhibitors in Perspective. Annals of Oncology, 30, 1437-1447. https://doi.org/10.1093/annonc/mdz192 |
| [72] | Ning, J. and Wakimoto, H. (2020) Therapeutic Application of PARP Inhibitors in Neuro-Oncology. Trends in Cancer, 6, 147-159. https://doi.org/10.1016/j.trecan.2019.12.004 |
| [73] | Sulkowski, P.L., Oeck, S., Dow, J., et al. (2020) Oncometabolites Suppress DNA Repair by Disrupting Local Chromatin Signalling. Nature, 582, 586-591. https://doi.org/10.1038/s41586-020-2363-0 |
| [74] | Wang, Y., Wild, A.T., Turcan, S., et al. (2020) Targeting Therapeutic Vulnerabilities with PARP Inhibition and Radiation in IDH-Mutant Gliomas and Cholangiocarcinomas. Science Advances, 6, eaaz3221.
https://doi.org/10.1126/sciadv.aaz3221 |
| [75] | Sim, H.W., McDonald, K.L., Lwin, Z., et al. (2021) A Randomized Phase II Trial of Veliparib, Radiotherapy, and Temozolomide in Patients with Unmethylated MGMT Glioblastoma: The VERTU Study. Neuro-Oncology, 23, 1736- 1749. https://doi.org/10.1093/neuonc/noab111 |
