Vanishree Rao, Gautam Kumar, R J A Vibhavari, Krishnadas Nandakumar, Nanasaheb Thorat, Mallikarjuna Rao Chamallamudi, Nitesh Kumar
{"title":"Temozolomide Resistance: A Multifarious Review on Mechanisms Beyond <i>O</i>-6-Methylguanine-DNA Methyltransferase.","authors":"Vanishree Rao, Gautam Kumar, R J A Vibhavari, Krishnadas Nandakumar, Nanasaheb Thorat, Mallikarjuna Rao Chamallamudi, Nitesh Kumar","doi":"10.2174/1871527321666220404180944","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy with the oral alkylating agent temozolomide still prevails as a linchpin in the therapeutic regimen of glioblastoma alongside radiotherapy. Because of the impoverished prognosis and sparse chemotherapeutic medicaments associated with glioblastoma, the burgeoning resistance to temozolomide has made the whole condition almost irremediable.</p><p><strong>Objective: </strong>The present review highlights the possible mechanisms of drug resistance following chemotherapy with temozolomide.</p><p><strong>Methods: </strong>The review summarizes the recent developments, as published in articles from Scopus, PubMed, and Web of Science search engines.</p><p><strong>Description: </strong>One of the prime resistance mediators, O-6-methylguanine-DNA methyltransferase, upon activation, removes temozolomide-induced methyl adducts bound to DNA and reinstates genomic integrity. In the bargain, neoteric advances in the conception of temozolomide resistance have opened the door to explore several potential mediators like indirect DNA repair systems, efflux mechanisms, epigenetic modulation, microenvironmental influences, and autophagy-apoptosis processes that constantly lead to the failure of chemotherapy.</p><p><strong>Conclusion: </strong>This review sheds light on recent discoveries, proposed theories, and clinical developments in the field of temozolomide resistance to summarize the complex and intriguing involvement of oncobiological pathways.</p>","PeriodicalId":10456,"journal":{"name":"CNS & neurological disorders drug targets","volume":"22 6","pages":"817-831"},"PeriodicalIF":2.7000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"3","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"CNS & neurological disorders drug targets","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/1871527321666220404180944","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 3
Abstract
Background: Chemotherapy with the oral alkylating agent temozolomide still prevails as a linchpin in the therapeutic regimen of glioblastoma alongside radiotherapy. Because of the impoverished prognosis and sparse chemotherapeutic medicaments associated with glioblastoma, the burgeoning resistance to temozolomide has made the whole condition almost irremediable.
Objective: The present review highlights the possible mechanisms of drug resistance following chemotherapy with temozolomide.
Methods: The review summarizes the recent developments, as published in articles from Scopus, PubMed, and Web of Science search engines.
Description: One of the prime resistance mediators, O-6-methylguanine-DNA methyltransferase, upon activation, removes temozolomide-induced methyl adducts bound to DNA and reinstates genomic integrity. In the bargain, neoteric advances in the conception of temozolomide resistance have opened the door to explore several potential mediators like indirect DNA repair systems, efflux mechanisms, epigenetic modulation, microenvironmental influences, and autophagy-apoptosis processes that constantly lead to the failure of chemotherapy.
Conclusion: This review sheds light on recent discoveries, proposed theories, and clinical developments in the field of temozolomide resistance to summarize the complex and intriguing involvement of oncobiological pathways.
背景:口服烷基化剂替莫唑胺的化疗仍然是治疗胶质母细胞瘤和放疗的关键。由于胶质母细胞瘤预后差，化疗药物稀少，对替莫唑胺的耐药性迅速增长，使整个病情几乎无法治愈。目的:综述替莫唑胺化疗后耐药的可能机制。方法:本文总结了Scopus、PubMed和Web of Science搜索引擎上发表的最新进展。描述:o -6-甲基鸟嘌呤-DNA甲基转移酶(O-6-methylguanine-DNA methyltransferase)是主要的耐药介质之一，一经激活，就能去除替莫唑胺诱导的与DNA结合的甲基加合物，并恢复基因组的完整性。在此过程中，替莫唑胺耐药概念的最新进展为探索一些潜在的介质打开了大门，如间接DNA修复系统、外排机制、表观遗传调节、微环境影响和自噬-凋亡过程，这些介质不断导致化疗失败。结论:本文综述了替莫唑胺耐药领域的最新发现、提出的理论和临床进展，总结了复杂而有趣的肿瘤生物学途径。
期刊介绍：
Aims & Scope
CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes.
CNS & Neurological Disorders - Drug Targets publishes guest edited thematic issues written by leaders in the field covering a range of current topics of CNS & neurological drug targets. The journal also accepts for publication original research articles, letters, reviews and drug clinical trial studies.
As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal is essential reading for all pharmaceutical scientists involved in drug discovery and development.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
