Rao Vanishree, Kumar Gautam, Vibhavari R J A, Nandakumar Krishnadas, Thorat Nanasaheb D, Chamallamudi Mallikarjuna Rao, Kumar Nitesh
Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, 576104, Karnataka, India.
Nuffield Department of Women's and Reproductive Health, John Radcliffe Hospital, Medical Sciences Division, University of Oxford, Oxford OX3 9DU, United Kingdom.
CNS Neurol Disord Drug Targets. 2023;22(6):817-831. doi: 10.2174/1871527321666220404180944.
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.
The present review highlights the possible mechanisms of drug resistance following chemotherapy with temozolomide.
The review summarizes the recent developments, as published in articles from Scopus, PubMed, and Web of Science search engines.
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.
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.
口服烷化剂替莫唑胺化疗仍是胶质母细胞瘤治疗方案中与放疗并驾齐驱的关键手段。由于胶质母细胞瘤预后不佳且化疗药物匮乏，对替莫唑胺迅速产生的耐药性使整个病情几乎无法挽救。
本综述重点介绍替莫唑胺化疗后耐药的可能机制。
本综述总结了Scopus、PubMed和Web of Science搜索引擎发表文章中的最新进展。
主要耐药介质之一O-6-甲基鸟嘌呤-DNA甲基转移酶激活后，可去除与DNA结合的替莫唑胺诱导的甲基加合物，恢复基因组完整性。同时，替莫唑胺耐药概念的新进展为探索多种潜在介质打开了大门，如间接DNA修复系统、外排机制、表观遗传调控、微环境影响以及自噬-凋亡过程，这些因素不断导致化疗失败。
本综述阐明了替莫唑胺耐药领域的最新发现、提出的理论和临床进展，以总结肿瘤生物学途径复杂而有趣的参与情况。
