A multifaceted review of temozolomide resistance mechanisms in glioblastoma beyond O-6-methylguanine-DNA methyltransferase
Temozolomide (TMZ), an oral alkylating agent, is a cornerstone of standard-of-care multimodality therapy for glioblastoma. In spite of significant efforts to treat this disease, the tumor carries a poor prognosis and is considered incurable largely due to the development of chemoresistance. One of t...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wolters Kluwer Medknow Publications
2019-01-01
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| Series: | Glioma |
| Subjects: | |
| Online Access: | http://www.jglioma.com/article.asp?issn=2589-6113;year=2019;volume=2;issue=2;spage=68;epage=82;aulast=Woo |
| _version_ | 1828346922153279488 |
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| author | Peter Y. M. Woo Yi Li Anna H. Y. Chan Stephanie C. P. Ng Herbert H. F. Loong Danny T. M. Chan George K. C. Wong Wai-Sang Poon |
| author_facet | Peter Y. M. Woo Yi Li Anna H. Y. Chan Stephanie C. P. Ng Herbert H. F. Loong Danny T. M. Chan George K. C. Wong Wai-Sang Poon |
| author_sort | Peter Y. M. Woo |
| collection | DOAJ |
| description | Temozolomide (TMZ), an oral alkylating agent, is a cornerstone of standard-of-care multimodality therapy for glioblastoma. In spite of significant efforts to treat this disease, the tumor carries a poor prognosis and is considered incurable largely due to the development of chemoresistance. One of the main mechanisms for this phenomenon is the activation of tumor DNA repair systems, such as O-6-methylguanine-DNA methyltransferase, that removes TMZ-induced DNA adducts and restores genomic integrity. Recent advances in the understanding of TMZ resistance oncobiology have introduced several novel independent molecular mechanisms involving epigenetic, transcriptomic, proteomic aberrations as well as alterations in apoptosis-autophagy processes, receptor tyrosine kinase activity, the tumor microenvironment, and the emergence of glioma stem cells. This article describes a multifaceted summary of the latest proposed causes for TMZ resistance and their complex interactions. It is believed that only by comprehending this growing network of interdependent mechanisms can effective combinatorial oncologic therapeutic strategies be developed to improve patient overall survival. |
| first_indexed | 2024-04-14T00:31:48Z |
| format | Article |
| id | doaj.art-3652e18040d640ffbf90f719b93ec390 |
| institution | Directory Open Access Journal |
| issn | 2589-6113 2589-6121 |
| language | English |
| last_indexed | 2024-04-14T00:31:48Z |
| publishDate | 2019-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Glioma |
| spelling | doaj.art-3652e18040d640ffbf90f719b93ec3902022-12-22T02:22:30ZengWolters Kluwer Medknow PublicationsGlioma2589-61132589-61212019-01-0122688210.4103/glioma.glioma_3_19A multifaceted review of temozolomide resistance mechanisms in glioblastoma beyond O-6-methylguanine-DNA methyltransferasePeter Y. M. WooYi LiAnna H. Y. ChanStephanie C. P. NgHerbert H. F. LoongDanny T. M. ChanGeorge K. C. WongWai-Sang PoonTemozolomide (TMZ), an oral alkylating agent, is a cornerstone of standard-of-care multimodality therapy for glioblastoma. In spite of significant efforts to treat this disease, the tumor carries a poor prognosis and is considered incurable largely due to the development of chemoresistance. One of the main mechanisms for this phenomenon is the activation of tumor DNA repair systems, such as O-6-methylguanine-DNA methyltransferase, that removes TMZ-induced DNA adducts and restores genomic integrity. Recent advances in the understanding of TMZ resistance oncobiology have introduced several novel independent molecular mechanisms involving epigenetic, transcriptomic, proteomic aberrations as well as alterations in apoptosis-autophagy processes, receptor tyrosine kinase activity, the tumor microenvironment, and the emergence of glioma stem cells. This article describes a multifaceted summary of the latest proposed causes for TMZ resistance and their complex interactions. It is believed that only by comprehending this growing network of interdependent mechanisms can effective combinatorial oncologic therapeutic strategies be developed to improve patient overall survival.http://www.jglioma.com/article.asp?issn=2589-6113;year=2019;volume=2;issue=2;spage=68;epage=82;aulast=WooGlioblastomaglioma stem cellshistone modificationmicroRNAO-6-methylguanine-DNA methyltransferasereceptor tyrosine kinaseresistancetemozolomide |
| spellingShingle | Peter Y. M. Woo Yi Li Anna H. Y. Chan Stephanie C. P. Ng Herbert H. F. Loong Danny T. M. Chan George K. C. Wong Wai-Sang Poon A multifaceted review of temozolomide resistance mechanisms in glioblastoma beyond O-6-methylguanine-DNA methyltransferase Glioma Glioblastoma glioma stem cells histone modification microRNA O-6-methylguanine-DNA methyltransferase receptor tyrosine kinase resistance temozolomide |
| title | A multifaceted review of temozolomide resistance mechanisms in glioblastoma beyond O-6-methylguanine-DNA methyltransferase |
| title_full | A multifaceted review of temozolomide resistance mechanisms in glioblastoma beyond O-6-methylguanine-DNA methyltransferase |
| title_fullStr | A multifaceted review of temozolomide resistance mechanisms in glioblastoma beyond O-6-methylguanine-DNA methyltransferase |
| title_full_unstemmed | A multifaceted review of temozolomide resistance mechanisms in glioblastoma beyond O-6-methylguanine-DNA methyltransferase |
| title_short | A multifaceted review of temozolomide resistance mechanisms in glioblastoma beyond O-6-methylguanine-DNA methyltransferase |
| title_sort | multifaceted review of temozolomide resistance mechanisms in glioblastoma beyond o 6 methylguanine dna methyltransferase |
| topic | Glioblastoma glioma stem cells histone modification microRNA O-6-methylguanine-DNA methyltransferase receptor tyrosine kinase resistance temozolomide |
| url | http://www.jglioma.com/article.asp?issn=2589-6113;year=2019;volume=2;issue=2;spage=68;epage=82;aulast=Woo |
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