{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:28:30Z","timestamp":1791584910588,"version":"4.3.4"},"reference-count":144,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Mayo Clinic, and the National Cancer Institute","award":["U19 CA264362"],"award-info":[{"award-number":["U19 CA264362"]}]},{"name":"Mayo Clinic, and the National Cancer Institute","award":["NIH R03 CA201612"],"award-info":[{"award-number":["NIH R03 CA201612"]}]},{"name":"Eagles 5th District Cancer Telethon- Cancer Research Fund, the Midwest RadOnc Clinical Innovations Award, and the Center of Innovation for Brain Tumor Therapeutics"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Temozolomide (TMZ) remains the cornerstone of chemotherapeutic agent for glioblastoma (GBM), yet intrinsic and acquired resistance severely limits its clinical benefit. While O6-methylguanine-DNA methyltransferase (MGMT)\u2013mediated repair of TMZ-induced O6-methylguanine (O6-meG) lesions has been extensively studied, the DNA mismatch repair (MMR) pathway is increasingly recognized as a key determinant of TMZ cytotoxicity. Canonical MMR, mediated by MutS\u03b1 (MSH2\u2013MSH6) and MutL\u03b1 (MLH1\u2013PMS2) complexes, recognizes O6-meG: thymine mispairs generated during replication and initiates futile repair cycles that culminate in replication stress, replication fork collapse, and apoptotic signaling; intact canonical MMR is, therefore, required for TMZ-induced cell death. Disruption of canonical MMR, frequently via acquired MSH6 mutations, confers TMZ tolerance and drives hypermutated recurrent GBM. Beyond mismatch correction, MMR proteins perform non-canonical functions in DNA damage signaling, replication stress responses, transcriptional regulation, chromatin dynamics, and immune modulation. These activities may shift the outcome from cytotoxic futile repair toward replication stress adaptation, Translesion synthesis (TLS)-mediated lesion tolerance, immune remodeling, and therapeutic resistance. Notably, partial attenuation or functional diversion of MMR may decouple lesion recognition from cytotoxic signaling, enabling TLS-mediated lesion tolerance without complete loss of MMR activity. This review integrates current insights into canonical and non-canonical MMR functions in GBM, defines their distinct contributions to TMZ sensitivity and resistance, and highlights therapeutic opportunities to exploit MMR-associated dependencies, including synthetic lethal strategies and immunotherapeutic vulnerabilities linked to MMR deficiency-driven hypermutation.<\/jats:p>","DOI":"10.3390\/ijms27146517","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T13:25:46Z","timestamp":1784726746000},"page":"6517","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Divergent Roles of Canonical and Non-Canonical Mismatch Repair in Regulating Temozolomide Sensitivity in Glioblastoma"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9107-9935","authenticated-orcid":false,"given":"Shiv K.","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teddy R.","family":"Friedman","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7489-4885","authenticated-orcid":false,"given":"Jann N.","family":"Sarkaria","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"655","DOI":"10.3171\/2019.5.JNS19364","article-title":"Molecular and cellular intratumoral heterogeneity in primary glioblastoma: Clinical and translational implications","volume":"133","author":"Bernstock","year":"2020","journal-title":"J. Neurosurg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1093\/annonc\/mdx169","article-title":"Intratumoral heterogeneity: Pathways to treatment resistance and relapse in human glioblastoma","volume":"28","author":"Qazi","year":"2017","journal-title":"Ann. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/S1470-2045(09)70025-7","article-title":"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","volume":"10","author":"Stupp","year":"2009","journal-title":"Lancet Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1056\/NEJMoa043330","article-title":"Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma","volume":"352","author":"Stupp","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"102","DOI":"10.2174\/1874467211205010102","article-title":"Temozolomide: Mechanisms of action, repair and resistance","volume":"5","author":"Zhang","year":"2012","journal-title":"Curr. Mol. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1038\/s41388-025-03454-5","article-title":"Post-translational modifications in DNA damage repair: Mechanisms underlying temozolomide resistance in glioblastoma","volume":"44","author":"Chen","year":"2025","journal-title":"Oncogene"},{"key":"ref_7","first-page":"17","article-title":"Mechanisms of temozolomide resistance in glioblastoma\u2014A comprehensive review","volume":"4","author":"Singh","year":"2021","journal-title":"Cancer Drug Resist."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1056\/NEJMoa043331","article-title":"MGMT gene silencing and benefit from temozolomide in glioblastoma","volume":"352","author":"Hegi","year":"2005","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.gendis.2016.04.007","article-title":"Temozolomide resistance in glioblastoma multiforme","volume":"3","author":"Lee","year":"2016","journal-title":"Genes Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1038\/nrneurol.2014.100","article-title":"MGMT testing\u2014The challenges for biomarker-based glioma treatment","volume":"10","author":"Wick","year":"2014","journal-title":"Nat. Rev. Neurol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1038\/sj.onc.1209785","article-title":"Apoptosis in malignant glioma cells triggered by the temozolomide-induced DNA lesion O6-methylguanine","volume":"26","author":"Roos","year":"2007","journal-title":"Oncogene"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yoshimoto, K., Mizoguchi, M., Hata, N., Murata, H., Hatae, R., Amano, T., Nakamizo, A., and Sasaki, T. (2012). Complex DNA repair pathways as possible therapeutic targets to overcome temozolomide resistance in glioblastoma. Front. Oncol., 2.","DOI":"10.3389\/fonc.2012.00186"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2038","DOI":"10.1158\/1078-0432.CCR-06-2149","article-title":"Loss of the mismatch repair protein MSH6 in human glioblastomas is associated with tumor progression during temozolomide treatment","volume":"13","author":"Cahill","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3987","DOI":"10.1158\/0008-5472.CAN-06-0127","article-title":"A hypermutation phenotype and somatic MSH6 mutations in recurrent human malignant gliomas after alkylator chemotherapy","volume":"66","author":"Hunter","year":"2006","journal-title":"Cancer Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4622","DOI":"10.1158\/1078-0432.CCR-08-3012","article-title":"MSH6 mutations arise in glioblastomas during temozolomide therapy and mediate temozolomide resistance","volume":"15","author":"Yip","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1126\/science.1239947","article-title":"Mutational analysis reveals the origin and therapy-driven evolution of recurrent glioma","volume":"343","author":"Johnson","year":"2014","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1038\/s41586-020-2209-9","article-title":"Mechanisms and therapeutic implications of hypermutation in gliomas","volume":"580","author":"Touat","year":"2020","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Yaacov, A., Gillis, R., Salim, J., Katz, D., Asna, N., Paldor, I., and Grinshpun, A. (2025). The Temozolomide Mutational Signature: Mechanisms, Clinical Implications, and Therapeutic Opportunities in Primary Brain Tumor Management. Cells, 15.","DOI":"10.3390\/cells15010057"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1002\/ijc.26083","article-title":"Promoter methylation and expression of MGMT and the DNA mismatch repair genes MLH1, MSH2, MSH6 and PMS2 in paired primary and recurrent glioblastomas","volume":"129","author":"Felsberg","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4894","DOI":"10.1158\/1078-0432.CCR-13-1856","article-title":"Novel MSH6 mutations in treatment-naive glioblastoma and anaplastic oligodendroglioma contribute to temozolomide resistance independently of MGMT promoter methylation","volume":"20","author":"Nguyen","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1038\/nrm1907","article-title":"The multifaceted mismatch-repair system","volume":"7","author":"Jiricny","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/j.dnarep.2004.06.006","article-title":"Mismatch repair and DNA damage signalling","volume":"3","author":"Stojic","year":"2004","journal-title":"DNA Repair"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"102918","DOI":"10.1016\/j.dnarep.2020.102918","article-title":"DNA mismatch repair in the chromatin context: Mechanisms and therapeutic potential","volume":"93","author":"Huang","year":"2020","journal-title":"DNA Repair"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"a012633","DOI":"10.1101\/cshperspect.a012633","article-title":"Postreplicative mismatch repair","volume":"5","author":"Jiricny","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/cr.2007.115","article-title":"Mechanisms and functions of DNA mismatch repair","volume":"18","author":"Li","year":"2008","journal-title":"Cell Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5107","DOI":"10.1158\/1078-0432.CCR-10-0821","article-title":"Therapeutic targeting of the DNA mismatch repair pathway","volume":"16","author":"Martin","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Pecina-Slaus, N., Kafka, A., Salamon, I., and Bukovac, A. (2020). Mismatch Repair Pathway, Genome Stability and Cancer. Front. Mol. Biosci., 7.","DOI":"10.3389\/fmolb.2020.00122"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"14324","DOI":"10.3390\/cimb46120859","article-title":"Towards Effective Treatment of Glioblastoma: The Role of Combination Therapies and the Potential of Phytotherapy and Micotherapy","volume":"46","author":"Gaiaschi","year":"2024","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Gaiaschi, L., De Luca, F., Roda, E., Ferrari, B., Casali, C., Inguscio, C.R., Gola, F., Pelloni, E., Savino, E., and Ravera, M. (2024). A Phyto-mycotherapeutic Supplement, Namely Ganostile, as Effective Adjuvant in Brain Cancer Management: An In Vitro Study Using U251 Human Glioblastoma Cell Line. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25116204"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1007\/s10495-023-01857-x","article-title":"Study on the activation of cell death mechanisms: In search of new therapeutic targets in glioblastoma multiforme","volume":"28","author":"Gaiaschi","year":"2023","journal-title":"Apoptosis"},{"key":"ref_31","first-page":"2585","article-title":"Temozolomide and treatment of malignant glioma","volume":"6","author":"Friedman","year":"2000","journal-title":"Clin. Cancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1038\/nrc3185","article-title":"Balancing repair and tolerance of DNA damage caused by alkylating agents","volume":"12","author":"Fu","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"354","DOI":"10.5414\/CPP40354","article-title":"DNA repair in resistance to alkylating anticancer drugs","volume":"40","author":"Kaina","year":"2002","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"a012583","DOI":"10.1101\/cshperspect.a012583","article-title":"Base excision repair","volume":"5","author":"Krokan","year":"2013","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"103303","DOI":"10.1016\/j.dnarep.2022.103303","article-title":"Double-strand breaks: When DNA repair events accidentally meet","volume":"112","author":"Fujii","year":"2022","journal-title":"DNA Repair"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1158\/1078-0432.CCR-19-2000","article-title":"Restoration of Temozolomide Sensitivity by PARP Inhibitors in Mismatch Repair Deficient Glioblastoma is Independent of Base Excision Repair","volume":"26","author":"Higuchi","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1111\/gtc.12929","article-title":"XRCC1 counteracts poly(ADP ribose)polymerase (PARP) poisons, olaparib and talazoparib, and a clinical alkylating agent, temozolomide, by promoting the removal of trapped PARP1 from broken DNA","volume":"27","author":"Hirota","year":"2022","journal-title":"Genes Cells"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1038\/nrn2559","article-title":"DNA repair deficiency and neurological disease","volume":"10","author":"McKinnon","year":"2009","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1038\/s41556-021-00792-w","article-title":"XRCC1 protects transcription from toxic PARP1 activity during DNA base excision repair","volume":"23","author":"Adamowicz","year":"2021","journal-title":"Nat. Cell Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1016\/j.dnarep.2007.03.008","article-title":"MGMT: Key node in the battle against genotoxicity, carcinogenicity and apoptosis induced by alkylating agents","volume":"6","author":"Kaina","year":"2007","journal-title":"DNA Repair"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1002\/bies.950161110","article-title":"DNA damage tolerance, mismatch repair and genome instability","volume":"16","author":"Karran","year":"1994","journal-title":"Bioessays"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.molmed.2006.07.007","article-title":"DNA damage-induced cell death by apoptosis","volume":"12","author":"Roos","year":"2006","journal-title":"Trends Mol. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"168","DOI":"10.4161\/cc.9.1.10363","article-title":"Processing of O6-methylguanine into DNA double-strand breaks requires two rounds of replication whereas apoptosis is also induced in subsequent cell cycles","volume":"9","author":"Quiros","year":"2010","journal-title":"Cell Cycle"},{"key":"ref_44","first-page":"53","article-title":"Structural, molecular and cellular functions of MSH2 and MSH6 during DNA mismatch repair, damage signaling and other noncanonical activities","volume":"743\u2013744","author":"Edelbrock","year":"2013","journal-title":"Mutat. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e69544","DOI":"10.7554\/eLife.69544","article-title":"Crosstalk between repair pathways elicits double-strand breaks in alkylated DNA and implications for the action of temozolomide","volume":"10","author":"Fuchs","year":"2021","journal-title":"eLife"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"12","DOI":"10.6004\/jnccn.2023.0002","article-title":"NCCN Guidelines(R) Insights: Central Nervous System Cancers, Version 2.2022","volume":"21","author":"Horbinski","year":"2023","journal-title":"J. Natl. Compr. Canc. Netw."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/s41571-020-00447-z","article-title":"EANO guidelines on the diagnosis and treatment of diffuse gliomas of adulthood","volume":"18","author":"Weller","year":"2021","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1215\/15228517-2009-001","article-title":"Identification of regions correlating MGMT promoter methylation and gene expression in glioblastomas","volume":"11","author":"Everhard","year":"2009","journal-title":"Neuro Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.trecan.2020.02.010","article-title":"MGMT Status as a Clinical Biomarker in Glioblastoma","volume":"6","author":"Butler","year":"2020","journal-title":"Trends Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2949","DOI":"10.1038\/s41467-018-05373-4","article-title":"A novel enhancer regulates MGMT expression and promotes temozolomide resistance in glioblastoma","volume":"9","author":"Chen","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1158\/1078-0432.CCR-18-3181","article-title":"MGMT Promoter Methylation Cutoff with Safety Margin for Selecting Glioblastoma Patients into Trials Omitting Temozolomide: A Pooled Analysis of Four Clinical Trials","volume":"25","author":"Hegi","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3127","DOI":"10.1158\/0008-5472.CAN-14-3616","article-title":"Minor Changes in Expression of the Mismatch Repair Protein MSH2 Exert a Major Impact on Glioblastoma Response to Temozolomide","volume":"75","author":"Braun","year":"2015","journal-title":"Cancer Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4234","DOI":"10.1158\/0008-5472.CAN-22-2036","article-title":"MEX3A Impairs DNA Mismatch Repair Signaling and Mediates Acquired Temozolomide Resistance in Glioblastoma","volume":"82","author":"Gan","year":"2022","journal-title":"Cancer Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1158\/0008-5472.CAN-16-2983","article-title":"Temozolomide in the Era of Precision Medicine","volume":"77","author":"Thomas","year":"2017","journal-title":"Cancer Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.cell.2006.05.039","article-title":"Endonucleolytic function of MutLalpha in human mismatch repair","volume":"126","author":"Kadyrov","year":"2006","journal-title":"Cell"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.molcel.2006.04.023","article-title":"ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts","volume":"22","author":"Yoshioka","year":"2006","journal-title":"Mol. Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3342","DOI":"10.1101\/gad.455407","article-title":"Mismatch repair-dependent processing of methylation damage gives rise to persistent single-stranded gaps in newly replicated DNA","volume":"21","author":"Mojas","year":"2007","journal-title":"Genes Dev."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Caccese, M., Ius, T., Simonelli, M., Fassan, M., Cesselli, D., Dipasquale, A., Cavallin, F., Padovan, M., Salvalaggio, A., and Gardiman, M.P. (2020). Mismatch-Repair Protein Expression in High-Grade Gliomas: A Large Retrospective Multicenter Study. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186716"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4859","DOI":"10.1158\/1078-0432.CCR-07-4807","article-title":"Mismatch repair deficiency does not mediate clinical resistance to temozolomide in malignant glioma","volume":"14","author":"Maxwell","year":"2008","journal-title":"Clin. Cancer Res."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"11557","DOI":"10.1074\/jbc.M900908200","article-title":"Distinct nucleotide binding\/hydrolysis properties and molar ratio of MutSalpha and MutSbeta determine their differential mismatch binding activities","volume":"284","author":"Tian","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"5827","DOI":"10.1038\/s41598-022-09614-x","article-title":"Mismatch repair proteins play a role in ATR activation upon temozolomide treatment in MGMT-methylated glioblastoma","volume":"12","author":"Ganesa","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1523","DOI":"10.1073\/pnas.1720355115","article-title":"ATR-Chk1 activation mitigates replication stress caused by mismatch repair-dependent processing of DNA damage","volume":"115","author":"Gupta","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4331","DOI":"10.1158\/0008-5472.CAN-18-3394","article-title":"Temozolomide Sensitizes MGMT-Deficient Tumor Cells to ATR Inhibitors","volume":"79","author":"Jackson","year":"2019","journal-title":"Cancer Res."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1158\/0008-5472.CAN-15-1884","article-title":"The Error-Prone DNA Polymerase kappa Promotes Temozolomide Resistance in Glioblastoma through Rad17-Dependent Activation of ATR-Chk1 Signaling","volume":"76","author":"Peng","year":"2016","journal-title":"Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1101\/gad.351084.123","article-title":"ATR inhibition induces synthetic lethality in mismatch repair-deficient cells and augments immunotherapy","volume":"37","author":"Wang","year":"2023","journal-title":"Genes Dev."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"eadj5962","DOI":"10.1126\/scitranslmed.adj5962","article-title":"Aberrant ATM signaling and homology-directed DNA repair as a vulnerability of p53-mutant GBM to AZD1390-mediated radiosensitization","volume":"16","author":"Chen","year":"2024","journal-title":"Sci. Transl. Med."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1038\/s41467-024-45979-5","article-title":"Trans-lesion synthesis and mismatch repair pathway crosstalk defines chemoresistance and hypermutation mechanisms in glioblastoma","volume":"15","author":"Cheng","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1158\/1541-7786.MCR-16-0125","article-title":"Augmented HR Repair Mediates Acquired Temozolomide Resistance in Glioblastoma","volume":"14","author":"Todorova","year":"2016","journal-title":"Mol. Cancer Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"eadk2685","DOI":"10.1126\/sciadv.adk2685","article-title":"MutSbeta-MutLbeta-FANCJ axis mediates the restart of DNA replication after fork stalling at cotranscriptional G4\/R-loops","volume":"10","author":"Isik","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1016\/j.cell.2013.03.025","article-title":"The histone mark H3K36me3 regulates human DNA mismatch repair through its interaction with MutSalpha","volume":"153","author":"Li","year":"2013","journal-title":"Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"6870","DOI":"10.1073\/pnas.95.12.6870","article-title":"Incidence and functional consequences of hMLH1 promoter hypermethylation in colorectal carcinoma","volume":"95","author":"Herman","year":"1998","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"102102","DOI":"10.1016\/j.jbc.2022.102102","article-title":"Interplay between H3K36me3, methyltransferase SETD2, and mismatch recognition protein MutSalpha facilitates processing of oxidative DNA damage in human cells","volume":"298","author":"Guo","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1038\/s43018-022-00475-x","article-title":"A single-cell atlas of glioblastoma evolution under therapy reveals cell-intrinsic and cell-extrinsic therapeutic targets","volume":"3","author":"Wang","year":"2022","journal-title":"Nat. Cancer"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2584","DOI":"10.1091\/mbc.E18-10-0650","article-title":"NAD+ consumption by PARP1 in response to DNA damage triggers metabolic shift critical for damaged cell survival","volume":"30","author":"Murata","year":"2019","journal-title":"Mol. Biol. Cell"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1774","DOI":"10.1038\/s41556-023-01280-z","article-title":"NAD+ regulates nucleotide metabolism and genomic DNA replication","volume":"25","author":"Munk","year":"2023","journal-title":"Nat. Cell Biol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"3792","DOI":"10.1002\/1878-0261.13227","article-title":"Targeting the DNA damage response and repair in cancer through nucleotide metabolism","volume":"16","author":"Helleday","year":"2022","journal-title":"Mol. Oncol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1360","DOI":"10.1093\/nar\/gkq829","article-title":"Mechanisms of mutagenesis in vivo due to imbalanced dNTP pools","volume":"39","author":"Kumar","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5749","DOI":"10.1073\/pnas.0812715106","article-title":"The mismatch repair system promotes DNA polymerase zeta-dependent translesion synthesis in yeast","volume":"106","author":"Lehner","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.ccell.2020.11.006","article-title":"DNA Sensing in Mismatch Repair-Deficient Tumor Cells Is Essential for Anti-tumor Immunity","volume":"39","author":"Lu","year":"2021","journal-title":"Cancer Cell"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e163452","DOI":"10.1172\/JCI163452","article-title":"Understanding and therapeutically exploiting cGAS\/STING signaling in glioblastoma","volume":"134","author":"Low","year":"2024","journal-title":"J. Clin. Investig."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"103715","DOI":"10.1016\/j.dnarep.2024.103715","article-title":"Human translesion DNA polymerases iota and kappa mediate tolerance to temozolomide in MGMT-deficient glioblastoma cells","volume":"141","author":"Latancia","year":"2024","journal-title":"DNA Repair"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.cell.2019.05.028","article-title":"A Small Molecule Targeting Mutagenic Translesion Synthesis Improves Chemotherapy","volume":"178","author":"Wojtaszek","year":"2019","journal-title":"Cell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"10312","DOI":"10.1093\/nar\/gkt793","article-title":"Mismatch repair protein MSH2 regulates translesion DNA synthesis following exposure of cells to UV radiation","volume":"41","author":"Lv","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"103755","DOI":"10.1016\/j.dnarep.2024.103755","article-title":"DNA mismatch repair controls the mutagenicity of Polymerase zeta-dependent translesion synthesis at methylated guanines","volume":"142","author":"Mingard","year":"2024","journal-title":"DNA Repair"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"8001","DOI":"10.1128\/MCB.20.21.8001-8007.2000","article-title":"Replication past O(6)-methylguanine by yeast and human DNA polymerase eta","volume":"20","author":"Haracska","year":"2000","journal-title":"Mol. Cell Biol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"19701","DOI":"10.1073\/pnas.0609580103","article-title":"The structural basis for the mutagenicity of O6-methyl-guanine lesions","volume":"103","author":"Warren","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1128\/MCB.00993-09","article-title":"Differential roles for DNA polymerases eta, zeta, and REV1 in lesion bypass of intrastrand versus interstrand DNA cross-links","volume":"30","author":"Hicks","year":"2010","journal-title":"Mol. Cell Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1158\/1538-7445.AM2017-1109","article-title":"Abstract 1109: MutS\u03b1 and MutS\u03b2 mismatch repair complexes differentially regulate temozolomide efficacy & sensitizing effects of veliparib in glioblastoma cells","volume":"77","author":"Gupta","year":"2017","journal-title":"Cancer Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1074\/jbc.C200627200","article-title":"Transfer of the MSH2.MSH6 complex from proliferating cell nuclear antigen to mispaired bases in DNA","volume":"278","author":"Lau","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"6826","DOI":"10.1093\/nar\/gkz441","article-title":"Effective mismatch repair depends on timely control of PCNA retention on DNA by the Elg1 complex","volume":"47","author":"Gaubitz","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"pgae242","DOI":"10.1093\/pnasnexus\/pgae242","article-title":"Dual role of proliferating cell nuclear antigen monoubiquitination in facilitating Fanconi anemia-mediated interstrand crosslink repair","volume":"3","author":"Shah","year":"2024","journal-title":"PNAS Nexus"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1458","DOI":"10.1093\/neuonc\/noz129","article-title":"Molecular profiling of long-term IDH-wildtype glioblastoma survivors","volume":"21","author":"Burgenske","year":"2019","journal-title":"Neuro Oncol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"11144","DOI":"10.1074\/jbc.RA119.009054","article-title":"Repair and translesion synthesis of O6-alkylguanine DNA lesions in human cells","volume":"294","author":"Du","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e100","DOI":"10.1093\/nar\/gnh098","article-title":"Measurement of DNA mismatch repair activity in live cells","volume":"32","author":"Lei","year":"2004","journal-title":"Nucleic Acids Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"E1823","DOI":"10.1073\/pnas.1401182111","article-title":"Multiplexed DNA repair assays for multiple lesions and multiple doses via transcription inhibition and transcriptional mutagenesis","volume":"111","author":"Nagel","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_96","first-page":"111779","article-title":"Novel plasmids for the fluorescence-based evaluation of DNA mismatch repair in human cells","volume":"824","author":"Takedachi","year":"2022","journal-title":"Mutat. Res."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1007\/s00401-020-02226-7","article-title":"Patient-derived organoids and orthotopic xenografts of primary and recurrent gliomas represent relevant patient avatars for precision oncology","volume":"140","author":"Golebiewska","year":"2020","journal-title":"Acta Neuropathol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.cell.2019.11.036","article-title":"A Patient-Derived Glioblastoma Organoid Model and Biobank Recapitulates Inter- and Intra-tumoral Heterogeneity","volume":"180","author":"Jacob","year":"2020","journal-title":"Cell"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1327","DOI":"10.1038\/s41416-023-02402-y","article-title":"Ex vivo drug sensitivity screening predicts response to temozolomide in glioblastoma patients and identifies candidate biomarkers","volume":"129","author":"Ntafoulis","year":"2023","journal-title":"Br. J. Cancer"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Miramova, A., Gartner, A., and Ivanov, D. (2024). How to sensitize glioblastomas to temozolomide chemotherapy: A gap-centered view. Front. Cell Dev. Biol., 12.","DOI":"10.3389\/fcell.2024.1436563"},{"key":"ref_101","first-page":"5843","article-title":"Abrogation of the Chk1-mediated G2 checkpoint pathway potentiates temozolomide-induced toxicity in a p53-independent manner in human glioblastoma cells","volume":"61","author":"Hirose","year":"2001","journal-title":"Cancer Res."},{"key":"ref_102","first-page":"vdad165","article-title":"MGMT function determines the differential response of ATR inhibitors with DNA-damaging agents in glioma stem cells for GBM therapy","volume":"6","author":"Leong","year":"2024","journal-title":"Neurooncol. Adv."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.celrep.2015.12.032","article-title":"Cancer-Specific Synthetic Lethality between ATR and CHK1 Kinase Activities","volume":"14","author":"Sanjiv","year":"2016","journal-title":"Cell Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1038\/nature14184","article-title":"Homologous-recombination-deficient tumours are dependent on Poltheta-mediated repair","volume":"518","author":"Ceccaldi","year":"2015","journal-title":"Nature"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"3636","DOI":"10.1038\/s41467-021-23463-8","article-title":"Poltheta inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance","volume":"12","author":"Zatreanu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"4286","DOI":"10.1038\/s41467-019-12234-1","article-title":"Genetic determinants of cellular addiction to DNA polymerase theta","volume":"10","author":"Feng","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Barszczewska-Pietraszek, G., Czarny, P., Drzewiecka, M., Blaszczyk, M., Radek, M., Synowiec, E., Wigner-Jeziorska, P., Sitarek, P., Szemraj, J., and Skorski, T. (2024). Poltheta Inhibitor (ART558) Demonstrates a Synthetic Lethal Effect with PARP and RAD52 Inhibitors in Glioblastoma Cells. Int. J. Mol. Sci., 25, Correction in Int. J. Mol. Sci. 2026, 27, 1327. https:\/\/doi.org\/10.3390\/ijms25179134.","DOI":"10.3390\/ijms27031327"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"5294","DOI":"10.1038\/s41467-024-49316-8","article-title":"ATM inhibition exploits checkpoint defects and ATM-dependent double strand break repair in TP53-mutant glioblastoma","volume":"15","author":"Laverty","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/1748-717X-8-65","article-title":"Evaluation of poly (ADP-ribose) polymerase inhibitor ABT-888 combined with radiotherapy and temozolomide in glioblastoma","volume":"8","author":"Barazzuol","year":"2013","journal-title":"Radiat. Oncol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1093\/neuonc\/noab111","article-title":"A randomized phase II trial of veliparib, radiotherapy, and temozolomide in patients with unmethylated MGMT glioblastoma: The VERTU study","volume":"23","author":"Sim","year":"2021","journal-title":"Neuro Oncol."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Gupta, S.K., Smith, E.J., Mladek, A.C., Tian, S., Decker, P.A., Kizilbash, S.H., Kitange, G.J., and Sarkaria, J.N. (2018). PARP Inhibitors for Sensitization of Alkylation Chemotherapy in Glioblastoma: Impact of Blood-Brain Barrier and Molecular Heterogeneity. Front. Oncol., 8.","DOI":"10.3389\/fonc.2018.00670"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1158\/1535-7163.MCT-17-0365","article-title":"Restricted Delivery of Talazoparib Across the Blood-Brain Barrier Limits the Sensitizing Effects of PARP Inhibition on Temozolomide Therapy in Glioblastoma","volume":"16","author":"Kizilbash","year":"2017","journal-title":"Mol. Cancer Ther."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"djv369","DOI":"10.1093\/jnci\/djv369","article-title":"Delineation of MGMT Hypermethylation as a Biomarker for Veliparib-Mediated Temozolomide-Sensitizing Therapy of Glioblastoma","volume":"108","author":"Gupta","year":"2016","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1007\/s11060-020-03461-4","article-title":"Epigenetic preconditioning with decitabine sensitizes glioblastoma to temozolomide via induction of MLH1","volume":"147","author":"Gallitto","year":"2020","journal-title":"J. Neurooncol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/s41419-022-04751-7","article-title":"Class I HDAC overexpression promotes temozolomide resistance in glioma cells by regulating RAD18 expression","volume":"13","author":"Hanisch","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"6731","DOI":"10.21873\/anticanres.13888","article-title":"Temozolomide-resistant Glioblastoma Depends on HDAC6 Activity Through Regulation of DNA Mismatch Repair","volume":"39","author":"Kim","year":"2019","journal-title":"Anticancer Res."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"1037","DOI":"10.1038\/s41419-022-05497-y","article-title":"BET protein inhibition sensitizes glioblastoma cells to temozolomide treatment by attenuating MGMT expression","volume":"13","author":"Tancredi","year":"2022","journal-title":"Cell Death Dis."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.annonc.2021.02.006","article-title":"High tumor mutation burden fails to predict immune checkpoint blockade response across all cancer types","volume":"32","author":"McGrail","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1935","DOI":"10.1093\/neuonc\/noac116","article-title":"Phase III trial of chemoradiotherapy with temozolomide plus nivolumab or placebo for newly diagnosed glioblastoma with methylated MGMT promoter","volume":"24","author":"Lim","year":"2022","journal-title":"Neuro Oncol."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.1001\/jamaoncol.2020.1024","article-title":"Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma: The CheckMate 143 Phase 3 Randomized Clinical Trial","volume":"6","author":"Reardon","year":"2020","journal-title":"JAMA Oncol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1200\/JCO.2016.66.6552","article-title":"Immune Checkpoint Inhibition for Hypermutant Glioblastoma Multiforme Resulting From Germline Biallelic Mismatch Repair Deficiency","volume":"34","author":"Bouffet","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_122","first-page":"vdac076","article-title":"Detection of temozolomide-induced hypermutation and response to PD-1 checkpoint inhibitor in recurrent glioblastoma","volume":"4","author":"Daniel","year":"2022","journal-title":"Neurooncol. Adv."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"e195189","DOI":"10.1172\/JCI195189","article-title":"Mismatch repair deficiency drives malignant progression and alters the tumor immune microenvironment in glioblastoma models","volume":"136","author":"Soni","year":"2026","journal-title":"J. Clin. Investig."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"4736","DOI":"10.1111\/cas.15141","article-title":"Lomustine and nimustine exert efficient antitumor effects against glioblastoma models with acquired temozolomide resistance","volume":"112","author":"Yamamuro","year":"2021","journal-title":"Cancer Sci."},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Sim, H.W., Galanis, E., and Khasraw, M. (2022). PARP Inhibitors in Glioma: A Review of Therapeutic Opportunities. Cancers, 14.","DOI":"10.3390\/cancers14041003"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Daniel, P., Sabri, S., Chaddad, A., Meehan, B., Jean-Claude, B., Rak, J., and Abdulkarim, B.S. (2019). Temozolomide Induced Hypermutation in Glioma: Evolutionary Mechanisms and Therapeutic Opportunities. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00041"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1038\/s41467-020-14642-0","article-title":"Heterogeneity of response to immune checkpoint blockade in hypermutated experimental gliomas","volume":"11","author":"Aslan","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"799","DOI":"10.2217\/imt-2021-0277","article-title":"Hypermutation as a potential predictive biomarker of immunotherapy efficacy in high-grade gliomas: A broken dream?","volume":"14","author":"Gatto","year":"2022","journal-title":"Immunotherapy"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"3043","DOI":"10.1093\/neuonc\/noaf192","article-title":"Revisiting an old therapy for new, promising combinations: Biology and perspectives of lomustine in glioma treatment","volume":"27","author":"Bellamy","year":"2025","journal-title":"Neuro Oncol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1126\/science.abn7570","article-title":"Mechanism-based design of agents that selectively target drug-resistant glioma","volume":"377","author":"Lin","year":"2022","journal-title":"Science"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.bbcan.2017.01.004","article-title":"Chloroethylating nitrosoureas in cancer therapy: DNA damage, repair and cell death signaling","volume":"1868","author":"Nikolova","year":"2017","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"18241","DOI":"10.1021\/jacs.3c06483","article-title":"Mechanism of Action of KL-50, a Candidate Imidazotetrazine for the Treatment of Drug-Resistant Brain Cancers","volume":"146","author":"Huseman","year":"2024","journal-title":"J. Am. Chem. Soc."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1093\/neuonc\/noae257","article-title":"The novel DNA cross-linking agent KL-50 is active against patient-derived models of new and recurrent post-temozolomide mismatch repair-deficient glioblastoma","volume":"27","author":"McCord","year":"2025","journal-title":"Neuro Oncol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"2665","DOI":"10.1158\/1535-7163.MCT-16-0176","article-title":"Targeting Homologous Recombination by Pharmacological Inhibitors Enhances the Killing Response of Glioblastoma Cells Treated with Alkylating Drugs","volume":"15","author":"Berte","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"102029","DOI":"10.1016\/j.ctrv.2020.102029","article-title":"How did lomustine become standard of care in recurrent glioblastoma?","volume":"87","author":"Weller","year":"2020","journal-title":"Cancer Treat. Rev."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1038\/s41592-024-02308-4","article-title":"Quantifying DNA replication speeds in single cells by scEdU-seq","volume":"21","author":"Geisenberger","year":"2024","journal-title":"Nat. Methods"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1101\/gad.2053211","article-title":"Analysis of protein dynamics at active, stalled, and collapsed replication forks","volume":"25","author":"Sirbu","year":"2011","journal-title":"Genes Dev."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/bs.mie.2017.03.019","article-title":"DNA Fiber Analysis: Mind the Gap!","volume":"591","author":"Quinet","year":"2017","journal-title":"Methods Enzymol."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"5193","DOI":"10.1091\/mbc.e08-07-0724","article-title":"Effect of proliferating cell nuclear antigen ubiquitination and chromatin structure on the dynamic properties of the Y-family DNA polymerases","volume":"19","author":"Sabbioneda","year":"2008","journal-title":"Mol. Biol. Cell"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1038\/emboj.2010.330","article-title":"ATM activates the pentose phosphate pathway promoting anti-oxidant defence and DNA repair","volume":"30","author":"Cosentino","year":"2011","journal-title":"EMBO J."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"eade7236","DOI":"10.1126\/sciadv.ade7236","article-title":"Ribonucleotide reductase regulatory subunit M2 drives glioblastoma TMZ resistance through modulation of dNTP production","volume":"9","author":"Perrault","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"4310","DOI":"10.1038\/s41388-019-0724-7","article-title":"AKT inhibition impairs PCNA ubiquitylation and triggers synthetic lethality in homologous recombination-deficient cells submitted to replication stress","volume":"38","author":"Villafanez","year":"2019","journal-title":"Oncogene"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"2910","DOI":"10.1158\/1538-7445.AM2025-2910","article-title":"Abstract 2910: Pamiparib-induced replication stress augments the efficacy of temozolomide in GBM PDX models","volume":"85","author":"Gupta","year":"2025","journal-title":"Cancer Res."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"1637","DOI":"10.1001\/jamaoncol.2024.4361","article-title":"Efficacy of Adding Veliparib to Temozolomide for Patients With MGMT-Methylated Glioblastoma: A Randomized Clinical Trial","volume":"10","author":"Sarkaria","year":"2024","journal-title":"JAMA Oncol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6517\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T13:27:45Z","timestamp":1784726865000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/14\/6517"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,22]]},"references-count":144,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["ijms27146517"],"URL":"https:\/\/doi.org\/10.3390\/ijms27146517","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,22]]}}}